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Cao JF, Zhang X, Xia Q, Hang K, Men J, Tian J, Liao D, Xia Z, Li K. Insights into curcumin's anticancer activity in pancreatic ductal adenocarcinoma: Experimental and computational evidence targeting HRAS, CCND1, EGFR and AKT1. Bioorg Chem 2025; 157:108264. [PMID: 39954354 DOI: 10.1016/j.bioorg.2025.108264] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2024] [Revised: 02/04/2025] [Accepted: 02/07/2025] [Indexed: 02/17/2025]
Abstract
PURPOSE Curcumin, as a natural polyphenolic compound, possesses antitumor, antioxidant properties and anti-inflammatory. Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor, and there is a lack of molecular mechanisms and therapeutic options regarding relevant therapeutic agents. Therefore, we investigated the mechanism of curcumin inhibiting pancreatic cancer growth by modulating proliferation of cells and cellular metabolism. METHODS Bioinformatics analysis was involved in analyzing the intersecting targets of curcumin and pancreatic ductal adenocarcinoma. The effect of curcumin on proliferation of PANC-1 cells was tested by CCK-8, and total RNA from PANC-1 was also analysed by transcriptome sequencing. Molecular docking was involved in verifying binding stability of curcumin to protein targets. Molecular dynamics simulated and evaluated binding free energy, hydrogen bonds and root mean square fluctuation of the complex. RESULTS PPI, GO and KEGG were involved in screening and analysing key interacting protein targets. 40 μg/mL curcumin significantly inhibited the growth and proliferation of PANC-1. Transcriptome sequencing results showed gene expression of Cyclin D1 (CCND1), AKT serine/threonine kinase 1 (AKT1), HRas proto-oncogene (HRAS), epidermal growth factor receptor (EGFR) was significantly down-regulated by curcumin treatment. Result of molecular dynamics and molecular docking inhibited the free binding energies of CCND1/Curcumin, HRAS/Curcumin, AKT1/Curcumin and EGFR/Curcumin were -21.13 ± 3.41 kcal/mol, -21.84 ± 4.38 kcal/mol, -20.61 ± 1.82 kcal/mol and -27.37 ± 1.94 kcal/mol, respectively. CONCLUSION We found curcumin may not only regulate cell cycle progression in PDAC and apoptosis by down-regulating HRAS, thereby inhibiting CCND1 and its downstream signaling pathways, but also inhibit energy metabolism reprogramming, Ras-RAF-MEK-ERK and other downstream signalling pathways by down-regulating EGFR and AKT1, thereby affecting tumor cell metastasis, survival and proliferation.
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Affiliation(s)
- Jun-Feng Cao
- College of Medicine, Southwest Jiaotong University, Chengdu 610031 Sichuan, China
| | - Xiao Zhang
- Chengdu Medical College, Chengdu 610500 Sichuan, China
| | - Qingjie Xia
- Institute of Neurological Diseases, Translation Neuroscience Center, West China Hospital, Sichuan University, Chengdu 610041 Sichuan, China
| | - Kuan Hang
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041 Sichuan, China
| | - Jie Men
- College of Medicine, Southwest Jiaotong University, Chengdu 610031 Sichuan, China
| | - Jin Tian
- College of Medicine, Southwest Jiaotong University, Chengdu 610031 Sichuan, China
| | - Dunshui Liao
- Institute of Neurological Diseases, Translation Neuroscience Center, West China Hospital, Sichuan University, Chengdu 610041 Sichuan, China
| | - Zengliang Xia
- Institute of Neurological Diseases, Translation Neuroscience Center, West China Hospital, Sichuan University, Chengdu 610041 Sichuan, China
| | - Kezhou Li
- College of Medicine, Southwest Jiaotong University, Chengdu 610031 Sichuan, China; Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041 Sichuan, China.
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Salehi AM, Torogi F, Jalilian FA, Amini R. The Potential Role of Curcumin as a Regulator of microRNA in Colorectal Cancer: A Systematic Review. Microrna 2025; 14:42-48. [PMID: 39279107 DOI: 10.2174/0122115366304114240904051429] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Revised: 07/22/2024] [Accepted: 08/19/2024] [Indexed: 09/18/2024]
Abstract
INTRODUCTION Curcumin is known as a bioactive component that is found in the rhizomes of Curcuma longa. Curcumin is well known for its chemo-preventive and anticancer properties. However, its anticancer mechanism in colorectal cancer treatment is unclear, and some studies have shown that many microRNAs (miRs) could be potential targets for curcumin in colorectal cancer (CRC) treatment, so there is a need for their integration and clarification. METHODS We systematically searched international databases, including PubMed, Scopus, and Web of Science, until July 2021 by using some relevant keywords. RESULTS The search resulted in 87 papers, among which there were 18 related articles. Curcumin was found to cause the upregulation of miR-497, miR-200c, miR-200b, miR-409-3p, miR-34, miR-126, miR-145, miR-206, miR-491, miR-141, miR-429, miR-101, and miR-15a and the downregulation of miR-21, miR-155, miR-221, miR-222, miR-17-5p, miR-130a, miR-27, and miR-20a. CONCLUSION The present review study suggests that curcumin may be useful as a novel therapeutic agent for CRC by altering the expression level of miRs.
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Affiliation(s)
- Amir Mohammad Salehi
- School of Medicine, Student Research Committee, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Fatemeh Torogi
- Research Center for Molecular Medicine, Institute of Cancer, Avicenna Health Research Institute (AHRI), Hamadan University of Medical Sciences, Hamadan, Iran
| | - Farid Azizi Jalilian
- Department of Virology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Razieh Amini
- Research Center for Molecular Medicine, Institute of Cancer, Avicenna Health Research Institute (AHRI), Hamadan University of Medical Sciences, Hamadan, Iran
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Yin Z, You B, Bai Y, Zhao Y, Liao S, Sun Y, Wu Y. Natural Compounds Derived from Plants on Prevention and Treatment of Renal Cell Carcinoma: A Literature Review. Adv Biol (Weinh) 2024; 8:e2300025. [PMID: 37607316 DOI: 10.1002/adbi.202300025] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Revised: 08/04/2023] [Indexed: 08/24/2023]
Abstract
Renal cell carcinoma (RCC) accounts for roughly 85% of all malignant kidney cancer. Therapeutic options for RCC have expanded rapidly over the past decade. Targeted therapy and immunotherapy have ushered in a new era of the treatment of RCC, which has facilitated the outcomes of RCC. However, the related adverse effects and drug resistance remain an urgent issue. Natural compounds are optional strategies to reduce mobility. Natural compounds are favored by clinicians and researchers due to their good tolerance and low economic burden. Many studies have explored the anti-RCC activity of natural products and revealed relevant mechanisms. In this article, the chemoprevention and therapeutic potential of natural compounds is reviewed and the mechanisms regarding natural compounds are explored.
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Affiliation(s)
- Zhenjie Yin
- Department of Urology, Affiliated Sanming First Hospital, Fujian Medical University, Sanming, Fujian, 365001, P. R. China
| | - Bingyong You
- Department of Urology, Affiliated Sanming First Hospital, Fujian Medical University, Sanming, Fujian, 365001, P. R. China
| | - Yuanyuan Bai
- Department of Urology, Affiliated Sanming First Hospital, Fujian Medical University, Sanming, Fujian, 365001, P. R. China
| | - Yu Zhao
- Department of Medical and Radiation Oncology, Affiliated Sanming First Hospital, Fujian Medical University, Sanming, Fujian, 365001, P. R. China
| | - Shangfan Liao
- Department of Urology, Affiliated Sanming First Hospital, Fujian Medical University, Sanming, Fujian, 365001, P. R. China
| | - Yingming Sun
- Department of Medical and Radiation Oncology, Affiliated Sanming First Hospital, Fujian Medical University, Sanming, Fujian, 365001, P. R. China
| | - Yongyang Wu
- Department of Urology, Affiliated Sanming First Hospital, Fujian Medical University, Sanming, Fujian, 365001, P. R. China
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Ayed A. The role of natural products versus miRNA in renal cell carcinoma: implications for disease mechanisms and diagnostic markers. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2024; 397:6417-6437. [PMID: 38691151 DOI: 10.1007/s00210-024-03121-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Accepted: 04/24/2024] [Indexed: 05/03/2024]
Abstract
Natural products are chemical compounds produced by living organisms. They are isolated and purified to determine their function and can potentially be used as therapeutic agents. The ability of some bioactive natural products to modify the course of cancer is fascinating and promising. In the past 50 years, there have been advancements in cancer therapy that have increased survival rates for localized tumors. However, there has been little progress in treating advanced renal cell carcinoma (RCC), which is resistant to radiation and chemotherapy. Oncogenes and tumor suppressors are two roles played by microRNAs (miRNAs). They are involved in important pathogenetic mechanisms like hypoxia and epithelial-mesenchymal transition (EMT); they control apoptosis, cell growth, migration, invasion, angiogenesis, and proliferation through target proteins involved in various signaling pathways. Depending on their expression pattern, miRNAs may identify certain subtypes of RCC or distinguish tumor tissue from healthy renal tissue. As diagnostic biomarkers of RCC, circulating miRNAs show promise. There is a correlation between the expression patterns of several miRNAs and the prognosis and diagnosis of patients with RCC. Potentially high-risk primary tumors may be identified by comparing original tumor tissue with metastases. Variations in miRNA expression between treatment-sensitive and therapy-resistant patients' tissues and serum allow for the estimation of responsiveness to target therapy. Our knowledge of miRNAs' function in RCC etiology has a tremendous uptick. Finding and validating their gene targets could have an immediate effect on creating anticancer treatments based on miRNAs. Several miRNAs have the potential to be used as biomarkers for diagnosis and prognosis. This review provides an in-depth analysis of the current knowledge regarding natural compounds and their modes of action in combating cancer. Also, this study aims to give information about the diagnostic and prognostic value of miRNAs as cancer biomarkers and their involvement in the pathogenesis of RCC.
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Affiliation(s)
- Abdullah Ayed
- Department of Surgery, College of Medicine, University of Bisha, P.O Box 551, 61922, Bisha, Saudi Arabia.
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Islam F, Nath N, Zehravi M, Khan J, Jashim SBT, Charde MS, Chakole RD, Kumar KP, Babu AK, Nainu F, Khan SL, Rab SO, Emran TB, Wilairatana P. Exploring the role of natural bioactive molecules in genitourinary cancers: how far has research progressed? NATURAL PRODUCTS AND BIOPROSPECTING 2023; 13:39. [PMID: 37843642 PMCID: PMC10579213 DOI: 10.1007/s13659-023-00400-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/15/2023] [Accepted: 09/17/2023] [Indexed: 10/17/2023]
Abstract
The primary approaches to treat cancerous diseases include drug treatment, surgical procedures, biotherapy, and radiation therapy. Chemotherapy has been the primary treatment for cancer for a long time, but its main drawback is that it kills cancerous cells along with healthy ones, leading to deadly adverse health effects. However, genitourinary cancer has become a concern in recent years as it is more common in middle-aged people. So, researchers are trying to find possible therapeutic options from natural small molecules due to the many drawbacks associated with chemotherapy and other radiation-based therapies. Plenty of research was conducted regarding genitourinary cancer to determine the promising role of natural small molecules. So, this review focused on natural small molecules along with their potential therapeutic targets in the case of genitourinary cancers such as prostate cancer, renal cancer, bladder cancer, testicular cancer, and so on. Also, this review states some ongoing or completed clinical evidence in this regard.
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Affiliation(s)
- Fahadul Islam
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, 1207, Bangladesh
| | - Nikhil Nath
- Department of Pharmacy, International Islamic University Chittagong, Kumira, Chittagong, 4318, Bangladesh
| | - Mehrukh Zehravi
- Department of Clinical Pharmacy, College of Dentistry & Pharmacy, Buraydah Private Colleges, Buraydah, 51418, Kingdom of Saudi Arabia.
| | - Jishan Khan
- Department of Pharmacy, International Islamic University Chittagong, Kumira, Chittagong, 4318, Bangladesh
| | - Sumiya Ben-Ta Jashim
- Department of Pharmacy, International Islamic University Chittagong, Kumira, Chittagong, 4318, Bangladesh
| | - Manoj Shrawan Charde
- Government College of Pharmacy, Vidyanagar, Karad, Satara, 415124, Maharashtra, India
| | - Rita Dadarao Chakole
- Government College of Pharmacy, Vidyanagar, Karad, Satara, 415124, Maharashtra, India
| | - K Praveen Kumar
- Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Govt. of NCT of Delhi, Delhi Pharmaceutical Sciences and Research University (DPSRU), Mehrauli-Badarpur Road, PushpVihar, Sector 3, New Delhi, 110017, India
| | - A Kishore Babu
- Ratnadeep College of Pharmacy, Ratnapur, Jamkhed, Ahmednagar, 413206, Maharashtra, India
| | - Firzan Nainu
- Department of Pharmacy, Faculty of Pharmacy, Hasanuddin University, Makassar, 90245, Indonesia
| | - Sharuk L Khan
- Department of Pharmaceutical Chemistry, N.B.S. Institute of Pharmacy, Ausa, 413520, Maharashtra, India
| | - Safia Obaidur Rab
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia
| | - Talha Bin Emran
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, 1207, Bangladesh.
- Department of Pathology and Laboratory Medicine, Warren Alpert Medical School & Legorreta Cancer Center, Brown University, Providence, RI, 02912, USA.
| | - Polrat Wilairatana
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, Thailand.
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Yue S, Feng X, Cai Y, Ibrahim SA, Liu Y, Huang W. Regulation of Tumor Apoptosis of Poriae cutis-Derived Lanostane Triterpenes by AKT/PI3K and MAPK Signaling Pathways In Vitro. Nutrients 2023; 15:4360. [PMID: 37892435 PMCID: PMC10610537 DOI: 10.3390/nu15204360] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Revised: 10/07/2023] [Accepted: 10/10/2023] [Indexed: 10/29/2023] Open
Abstract
Poria cocos is traditionally used as both food and medicine. Triterpenoids in Poria cocos have a wide range of pharmacological activities, such as diuretic, sedative and tonic properties. In this study, the anti-tumor activities of poricoic acid A (PAA) and poricoic acid B (PAB), purified by high-speed counter-current chromatography, as well as their mechanisms and signaling pathways, were investigated using a HepG2 cell model. After treatment with PAA and PAB on HepG2 cells, the apoptosis was obviously increased (p < 0.05), and the cell cycle arrested in the G2/M phase. Studies showed that PAA and PAB can also inhibit the occurrence and development of tumor cells by stimulating the generation of ROS in tumor cells and inhibiting tumor migration and invasion. Combined Polymerase Chain Reaction and computer simulation of molecular docking were employed to explore the mechanism of tumor proliferation inhibition by PAA and PAB. By interfering with phosphatidylinositol-3-kinase/protein kinase B, Mitogen-activated protein kinases and p53 signaling pathways; and further affecting the expression of downstream caspases; matrix metalloproteinase family, cyclin-dependent kinase -cyclin, Intercellular adhesion molecules-1, Vascular Cell Adhesion Molecule-1 and Cyclooxygenase -2, may be responsible for their anti-tumor activity. Overall, the results suggested that PAA and PAB induced apoptosis, halted the cell cycle, and inhibited tumor migration and invasion through multi-pathway interactions, which may serve as a potential therapeutic agent against cancer.
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Affiliation(s)
- Shuai Yue
- College of Food Science and Technology, Huazhong Agricultural University, Wuhan 430070, China;
| | - Xi Feng
- Department of Nutrition, Food Science and Packaging, San Jose State University, San Jose, CA 95192, USA;
| | - Yousheng Cai
- School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China;
| | - Salam A. Ibrahim
- Department of Family and Consumer Sciences, North Carolina A&T State University, 171 Carver Hall, Greensboro, NC 27411, USA;
| | - Ying Liu
- College of Food Science and Technology, Huazhong Agricultural University, Wuhan 430070, China;
| | - Wen Huang
- College of Food Science and Technology, Huazhong Agricultural University, Wuhan 430070, China;
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7
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Rezaei S, Nikpanjeh N, Rezaee A, Gholami S, Hashemipour R, Biavarz N, Yousefi F, Tashakori A, Salmani F, Rajabi R, Khorrami R, Nabavi N, Ren J, Salimimoghadam S, Rashidi M, Zandieh MA, Hushmandi K, Wang Y. PI3K/Akt signaling in urological cancers: Tumorigenesis function, therapeutic potential, and therapy response regulation. Eur J Pharmacol 2023; 955:175909. [PMID: 37490949 DOI: 10.1016/j.ejphar.2023.175909] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Revised: 07/01/2023] [Accepted: 07/11/2023] [Indexed: 07/27/2023]
Abstract
In addition to environmental conditions, lifestyle factors, and chemical exposure, aberrant gene expression and mutations involve in the beginning and development of urological tumors. Even in Western nations, urological malignancies are among the top causes of patient death, and their prevalence appears to be gender dependent. The prognosis for individuals with urological malignancies remains dismal and unfavorable due to the ineffectiveness of conventional treatment methods. PI3K/Akt is a popular biochemical mechanism that is activated in tumor cells as a result of PTEN loss. PI3K/Akt escalates growth and metastasis. Moreover, due to the increase in tumor cell viability caused by PI3K/Akt activation, cancer cells may acquire resistance to treatment. This review article examines the function of PI3K/Akt in major urological tumors including bladder, prostate, and renal tumors. In prostate, bladder, and kidney tumors, the level of PI3K and Akt are notably elevated. In addition, the activation of PI3K/Akt enhances the levels of Bcl-2 and XIAP, hence increasing the tumor cell survival rate. PI3K/Akt ] upregulates EMT pathways and matrix metalloproteinase expression to increase urological cancer metastasis. Furthermore, stimulation of PI3K/Akt results in drug- and radio-resistant cancers, but its suppression by anti-tumor drugs impedes the tumorigenesis.
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Affiliation(s)
- Sahar Rezaei
- Faculty of Veterinary Medicine, Islamic Azad University, Science and Research Branch, Tehran, Iran
| | - Negin Nikpanjeh
- Faculty of Veterinary Medicine, Islamic Azad University, Science and Research Branch, Tehran, Iran
| | - Aryan Rezaee
- Iran University of Medical Sciences, Tehran, Iran
| | - Sarah Gholami
- Young Researcher and Elite Club, Islamic Azad University, Babol Branch, Babol, Iran
| | - Reza Hashemipour
- Faculty of Veterinary Medicine, Islamic Azad University, Karaj Branch, Karaj, Iran
| | - Negin Biavarz
- Faculty of Veterinary Medicine, Islamic Azad University, Science and Research Branch, Tehran, Iran
| | - Farnaz Yousefi
- Department of Clinical Science, Faculty of Veterinary Medicine, Islamic Azad University, Science and Research Branch, Tehran, Iran
| | - Ali Tashakori
- Faculty of Veterinary Medicine, Islamic Azad University, Science and Research Branch, Tehran, Iran
| | - Farshid Salmani
- Faculty of Veterinary Medicine, Islamic Azad University, Science and Research Branch, Tehran, Iran
| | - Romina Rajabi
- Faculty of Veterinary Medicine, Islamic Azad University, Science and Research Branch, Tehran, Iran
| | - Ramin Khorrami
- Department of Food Hygiene and Quality Control, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
| | - Noushin Nabavi
- Department of Urologic Sciences and Vancouver Prostate Centre, University of British Columbia, V6H3Z6, Vancouver, BC, Canada
| | - Jun Ren
- Shanghai Institute of Cardiovascular Diseases, Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Shokooh Salimimoghadam
- Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran
| | - Mohsen Rashidi
- Department Pharmacology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran; The Health of Plant and Livestock Products Research Center, Mazandaran University of Medical Sciences, Sari, Iran.
| | - Mohammad Arad Zandieh
- Department of Food Hygiene and Quality Control, Division of Epidemiology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
| | - Kiavash Hushmandi
- Department of Food Hygiene and Quality Control, Division of Epidemiology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
| | - Yuzhuo Wang
- Department of Urologic Sciences and Vancouver Prostate Centre, University of British Columbia, V6H3Z6, Vancouver, BC, Canada.
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Wang X, Tian Y, Lin H, Cao X, Zhang Z. Curcumin induces apoptosis in human hepatocellular carcinoma cells by decreasing the expression of STAT3/VEGF/HIF-1α signaling. Open Life Sci 2023; 18:20220618. [PMID: 37333486 PMCID: PMC10276545 DOI: 10.1515/biol-2022-0618] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Revised: 04/01/2023] [Accepted: 04/26/2023] [Indexed: 06/20/2023] Open
Abstract
Curcumin is the most abundant derivative of turmeric rhizome. Although studies have proved that curcumin could inhibit the growth of tumors, its specific molecular mechanism has not yet been fully elucidated. This study aims to systematically elaborate the mechanisms of curcumin against hepatocellular carcinoma. The anti-tumor effect of curcumin was determined by the cell viability test. Flow cytometry was applied to examine the cell cycle and the apoptosis of cancer cells, and the cancer cell migration was detected by wound healing experiments. The expressions of signal transducers and activators of transcription 3 (STAT3), vascular endothelial growth factor (VEGF), and hypoxia-inducible factor-1α (HIF-1α) in cancer cells were examined by immunostaining and analyzed by the Image J analysis system. After treatment with curcumin, the apoptosis ratio of HepG2 cells increased significantly (P < 0.05). The proliferation of cancer cells was arrested at the S-phase cell cycle, and the migration of cancer cells was inhibited by the increasing concentration of curcumin, together with the decreasing expressions of STAT3, VEGF, and HIF-1α signaling pathways. The results indicate that curcumin could effectively inhibit the growth and migration of hepatocarcinoma cells by inducing cancer cell apoptosis, blocking the cancer cell cycle in the S phase, and reducing the expression of STAT3, VEGF, and HIF-1α signaling pathways.
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Affiliation(s)
- Xiaoping Wang
- Key Laboratory of High Altitude Hypoxia Environment and Life Health, School of Medicine, Xizang Minzu University, No. 6 Wenhui East Road, Weicheng District, Xianyang, 712082 Shaanxi, China
- Joint Laboratory for Research on Active Components and Pharmacological Mechanism of Tibetan, Materia Medica of Tibetan Medical Research Center of Tibet, School of Medicine, Xizang Minzu University, Xianyang, 712082 Shaanxi, China
| | - Yu Tian
- Key Laboratory of High Altitude Hypoxia Environment and Life Health, School of Medicine, Xizang Minzu University, No. 6 Wenhui East Road, Weicheng District, Xianyang, 712082 Shaanxi, China
- Joint Laboratory for Research on Active Components and Pharmacological Mechanism of Tibetan, Materia Medica of Tibetan Medical Research Center of Tibet, School of Medicine, Xizang Minzu University, Xianyang, 712082 Shaanxi, China
| | - Huanping Lin
- Key Laboratory of High Altitude Hypoxia Environment and Life Health, School of Medicine, Xizang Minzu University, No. 6 Wenhui East Road, Weicheng District, Xianyang, 712082 Shaanxi, China
- Joint Laboratory for Research on Active Components and Pharmacological Mechanism of Tibetan, Materia Medica of Tibetan Medical Research Center of Tibet, School of Medicine, Xizang Minzu University, Xianyang, 712082 Shaanxi, China
| | - Xiaolan Cao
- Key Laboratory of High Altitude Hypoxia Environment and Life Health, School of Medicine, Xizang Minzu University, No. 6 Wenhui East Road, Weicheng District, Xianyang, 712082 Shaanxi, China
- Joint Laboratory for Research on Active Components and Pharmacological Mechanism of Tibetan, Materia Medica of Tibetan Medical Research Center of Tibet, School of Medicine, Xizang Minzu University, Xianyang, 712082 Shaanxi, China
| | - Zhendong Zhang
- Key Laboratory of High Altitude Hypoxia Environment and Life Health, School of Medicine, Xizang Minzu University, No. 6 Wenhui East Road, Weicheng District, Xianyang, 712082 Shaanxi, China
- Joint Laboratory for Research on Active Components and Pharmacological Mechanism of Tibetan, Materia Medica of Tibetan Medical Research Center of Tibet, School of Medicine, Xizang Minzu University, Xianyang, 712082 Shaanxi, China
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Gu XJ, Li YJ, Wang F, Ye T. MiR-30e-3p inhibits gastric cancer development by negatively regulating THO complex 2 and PI3K/AKT/mTOR signaling. World J Gastrointest Oncol 2022; 14:2170-2182. [PMID: 36438699 PMCID: PMC9694264 DOI: 10.4251/wjgo.v14.i11.2170] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Revised: 09/05/2022] [Accepted: 10/12/2022] [Indexed: 11/15/2022] Open
Abstract
BACKGROUND Gastric cancer (GC) is a common type of digestive cancer with high morbidity and mortality rates worldwide. Considerable effort has been expended in understanding the mechanism of GC development and metastasis. The current study therefore explores the involvement of microRNAs in the regulation of GC progression.
AIM To explore the expression and function of miR-30e-3p in GC development.
METHODS MiR-30e-3p was found to be downregulated in GC, with low levels thereof predicting poor outcomes among patients with GC. Functionally, we revealed that miR-30e-3p suppressed cell growth and metastatic behaviors of GC cells. Bioinformatics analysis predicted that THO complex 2 (THOC2) was a direct target of miR-30e-3p, and the interaction between miR-30e-3p and THOC2 was further validated by a luciferase reporter assay.
RESULTS Our findings revealed that knockdown of THOC2 inhibited the growth and metastatic behaviors of GC cells. After investigating signaling pathways involved in miR-30e-3p regulation, we found that the miR-30e-3p/THOC2 axis regulated the PI3K/AKT/mTOR pathway in GC.
CONCLUSION Our findings suggest the novel functional axis miR-30e-3p/THOC2 is involved in GC development and progression. The miR-30e-3p/THOC2 axis could be utilized to develop new therapies against GC.
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Affiliation(s)
- Xiao-Jing Gu
- Department of Gastroenterology, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Prefecture, China
| | - Ya-Jun Li
- Department of Gastroenterology, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Prefecture, China
| | - Fang Wang
- Department of Gastroenterology, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Prefecture, China
| | - Ting Ye
- Department of Gastroenterology, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Prefecture, China
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10
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Hashemi M, Mirzaei S, Barati M, Hejazi ES, Kakavand A, Entezari M, Salimimoghadam S, Kalbasi A, Rashidi M, Taheriazam A, Sethi G. Curcumin in the treatment of urological cancers: Therapeutic targets, challenges and prospects. Life Sci 2022; 309:120984. [PMID: 36150461 DOI: 10.1016/j.lfs.2022.120984] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Revised: 09/09/2022] [Accepted: 09/17/2022] [Indexed: 11/26/2022]
Abstract
Urological cancers include bladder, prostate and renal cancers that can cause death in males and females. Patients with urological cancers are mainly diagnosed at an advanced disease stage when they also develop resistance to therapy or poor response. The use of natural products in the treatment of urological cancers has shown a significant increase. Curcumin has been widely used in cancer treatment due to its ability to trigger cell death and suppress metastasis. The beneficial effects of curcumin in the treatment of urological cancers is the focus of current review. Curcumin can induce apoptosis in the three types of urological cancers limiting their proliferative potential. Furthermore, curcumin can suppress invasion of urological cancers through EMT inhibition. Notably, curcumin decreases the expression of MMPs, therefore interfering with urological cancer metastasis. When used in combination with chemotherapy agents, curcumin displays synergistic effects in suppressing cancer progression. It can also be used as a chemosensitizer. Based on pre-clinical studies, curcumin administration is beneficial in the treatment of urological cancers and future clinical applications might be considered upon solving problems related to the poor bioavailability of the compound. To improve the bioavailability of curcumin and increase its therapeutic index in urological cancer suppression, nanostructures have been developed to favor targeted delivery.
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Affiliation(s)
- Mehrdad Hashemi
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Sepideh Mirzaei
- Department of Biology, Faculty of Science, Islamic Azad University, Science and Research Branch, Tehran, Iran
| | - Maryamsadat Barati
- Department of Biology, Faculty of Basic (Fundamental) Science, Shahr Qods Branch, Islamic Azad University, Tehran, Iran
| | - Elahe Sadat Hejazi
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Amirabbas Kakavand
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Maliheh Entezari
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Shokooh Salimimoghadam
- Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran
| | - Alireza Kalbasi
- Department of Pharmacy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, United States of America
| | - Mohsen Rashidi
- Department Pharmacology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran; The Health of Plant and Livestock Products Research Center, Mazandaran University of Medical Sciences, Sari, Iran.
| | - Afshin Taheriazam
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Department of Orthopedics, Faculty of medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
| | - Gautam Sethi
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore; NUS Centre for Cancer Research, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore.
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11
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Bajalia EM, Azzouz FB, Chism DA, Giansiracusa DM, Wong CG, Plaskett KN, Bishayee A. Phytochemicals for the Prevention and Treatment of Renal Cell Carcinoma: Preclinical and Clinical Evidence and Molecular Mechanisms. Cancers (Basel) 2022; 14:3278. [PMID: 35805049 PMCID: PMC9265746 DOI: 10.3390/cancers14133278] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Revised: 06/26/2022] [Accepted: 06/30/2022] [Indexed: 11/18/2022] Open
Abstract
Renal cell carcinoma (RCC) is associated with about 90% of renal malignancies, and its incidence is increasing globally. Plant-derived compounds have gained significant attention in the scientific community for their preventative and therapeutic effects on cancer. To evaluate the anticancer potential of phytocompounds for RCC, we compiled a comprehensive and systematic review of the available literature. Our work was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. The literature search was performed using scholarly databases such as PubMed, Scopus, and ScienceDirect and keywords such as renal cell carcinoma, phytochemicals, cancer, tumor, proliferation, apoptosis, prevention, treatment, in vitro, in vivo, and clinical studies. Based on in vitro results, various phytochemicals, such as phenolics, terpenoids, alkaloids, and sulfur-containing compounds, suppressed cell viability, proliferation and growth, showed cytotoxic activity, inhibited invasion and migration, and enhanced the efficacy of chemotherapeutic drugs in RCC. In various animal tumor models, phytochemicals suppressed renal tumor growth, reduced tumor size, and hindered angiogenesis and metastasis. The relevant antineoplastic mechanisms involved upregulation of caspases, reduction in cyclin activity, induction of cell cycle arrest and apoptosis via modulation of a plethora of cell signaling pathways. Clinical studies demonstrated a reduced risk for the development of kidney cancer and enhancement of the efficacy of chemotherapeutic drugs. Both preclinical and clinical studies displayed significant promise of utilizing phytochemicals for the prevention and treatment of RCC. Further research, confirming the mechanisms and regulatory pathways, along with randomized controlled trials, are needed to establish the use of phytochemicals in clinical practice.
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Affiliation(s)
| | | | | | | | | | | | - Anupam Bishayee
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USA; (E.M.B.); (F.B.A.); (D.A.C.); (D.M.G.); (C.G.W.); (K.N.P.)
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12
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Guerreiro Í, Ferreira-Pêgo C, Carregosa D, Santos CN, Menezes R, Fernandes AS, Costa JG. Polyphenols and Their Metabolites in Renal Diseases: An Overview. Foods 2022; 11:foods11071060. [PMID: 35407148 PMCID: PMC8997953 DOI: 10.3390/foods11071060] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Revised: 04/01/2022] [Accepted: 04/04/2022] [Indexed: 12/12/2022] Open
Abstract
Kidney diseases constitute a worldwide public health problem, contributing to morbidity and mortality. The present study aimed to provide an overview of the published data regarding the potential beneficial effects of polyphenols on major kidney diseases, namely acute kidney injury, chronic kidney disease, diabetic nephropathy, renal cancer, and drug-induced nephrotoxicity. This study consists of a bibliographical review including in vitro and in vivo studies dealing with the effects of individual compounds. An analysis of the polyphenol metabolome in human urine was also conducted to estimate those compounds that are most likely to be responsible for the kidney protective effects of polyphenols. The biological effects of polyphenols can be highly attributed to the modulation of specific signaling cascades including those involved in oxidative stress responses, anti-inflammation processes, and apoptosis. There is increasing evidence that polyphenols afford great potential in renal disease protection. However, this evidence (especially when in vitro studies are involved) should be considered with caution before its clinical translation, particularly due to the unfavorable pharmacokinetics and extensive metabolization that polyphenols undergo in the human body. Future research should consider polyphenols and their metabolites that indeed reach kidney tissues.
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Affiliation(s)
- Íris Guerreiro
- CBIOS—Universidade Lusófona’s Research Center for Biosciences & Health Technologies, Campo Grande 376, 1749-024 Lisboa, Portugal; (Í.G.); (C.F.-P.); (R.M.); (A.S.F.)
| | - Cíntia Ferreira-Pêgo
- CBIOS—Universidade Lusófona’s Research Center for Biosciences & Health Technologies, Campo Grande 376, 1749-024 Lisboa, Portugal; (Í.G.); (C.F.-P.); (R.M.); (A.S.F.)
| | - Diogo Carregosa
- CEDOC, Chronic Diseases Research Center, NOVA Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Campo dos Mártires da Pátria, 130, 1169-056 Lisboa, Portugal; (D.C.); (C.N.S.)
| | - Cláudia N. Santos
- CEDOC, Chronic Diseases Research Center, NOVA Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Campo dos Mártires da Pátria, 130, 1169-056 Lisboa, Portugal; (D.C.); (C.N.S.)
| | - Regina Menezes
- CBIOS—Universidade Lusófona’s Research Center for Biosciences & Health Technologies, Campo Grande 376, 1749-024 Lisboa, Portugal; (Í.G.); (C.F.-P.); (R.M.); (A.S.F.)
- CEDOC, Chronic Diseases Research Center, NOVA Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Campo dos Mártires da Pátria, 130, 1169-056 Lisboa, Portugal; (D.C.); (C.N.S.)
- iBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2781-901 Oeiras, Portugal
| | - Ana S. Fernandes
- CBIOS—Universidade Lusófona’s Research Center for Biosciences & Health Technologies, Campo Grande 376, 1749-024 Lisboa, Portugal; (Í.G.); (C.F.-P.); (R.M.); (A.S.F.)
| | - João G. Costa
- CBIOS—Universidade Lusófona’s Research Center for Biosciences & Health Technologies, Campo Grande 376, 1749-024 Lisboa, Portugal; (Í.G.); (C.F.-P.); (R.M.); (A.S.F.)
- Correspondence:
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13
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Cruz-Gregorio A, Aranda-Rivera AK, Pedraza-Chaverri J, Solano JD, Ibarra-Rubio ME. Redox-sensitive signaling pathways in renal cell carcinoma. Biofactors 2022; 48:342-358. [PMID: 34590744 DOI: 10.1002/biof.1784] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Accepted: 09/07/2021] [Indexed: 12/24/2022]
Abstract
Renal cell carcinoma (RCC) is one of the most lethal urological cancers, highly resistant to chemo and radiotherapy. Obesity and smoking are the best-known risk factors of RCC, both related to oxidative stress presence, suggesting a significant role in RCC development and maintenance. Surgical resection is the treatment of choice for localized RCC; however, this neoplasia is hardly diagnosable at its initial stages, occurring commonly in late phases and even when metastasis is already present. Systemic therapies are the option against RCC in these more advanced stages, such as cytokine therapy or a combination of tyrosine kinase inhibitors with immunotherapies; nevertheless, these strategies are still insufficient. A field poorly analyzed in this neoplasia is the status of cell signaling pathways sensible to the redox state, which have been associated with the development and maintenance of RCC. This review focuses on alterations reported in the following redox-sensitive molecules and signaling pathways in RCC: mitogen-activated protein kinases, protein kinase B (AKT)/tuberous sclerosis complex 2/mammalian target of rapamycin C1, AKT/glycogen synthase kinase 3/β-catenin, nuclear factor κB/inhibitor of κB/epidermal growth factor receptor, and protein kinase Cζ/cut-like homeodomain protein/factor inhibiting hypoxia-inducible factor (HIF)/HIF as potential targets for redox therapy.
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Affiliation(s)
- Alfredo Cruz-Gregorio
- Laboratorio F-225, Departamento de Biología, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad de México, Mexico
| | - Ana Karina Aranda-Rivera
- Laboratorio F-315, Departamento de Biología, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad de México, Mexico
| | - José Pedraza-Chaverri
- Laboratorio F-315, Departamento de Biología, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad de México, Mexico
| | - José D Solano
- Laboratorio F-225, Departamento de Biología, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad de México, Mexico
| | - María Elena Ibarra-Rubio
- Laboratorio F-225, Departamento de Biología, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad de México, Mexico
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14
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Gong X, Jiang L, Li W, Liang Q, Li Z. Curcumin induces apoptosis and autophagy inhuman renal cell carcinoma cells via Akt/mTOR suppression. Bioengineered 2021; 12:5017-5027. [PMID: 34402718 PMCID: PMC8806675 DOI: 10.1080/21655979.2021.1960765] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Accepted: 07/22/2021] [Indexed: 01/20/2023] Open
Abstract
Renal cell carcinoma (RCC) is a highly aggressive cancer leading to high economic and social burden, and has increasing annual cases. Curcumin is a traditional Chinese medicine widely used as anti-inflammatory, anti-viral and anti-cancer agent, thus can be applicable in RCC therapy. The work assessed the effects of RCC treatment with Curcumin, Curcumin+3-MA, Curcumin+ CQ or curcumin+ Z-VAD in vitro and in vivo, and the mechanisms involved in inhibition of tumor cells proliferation. The study used ACHN tumor cells and C57BL/6 nude mice for results validation. Cell proliferation was determined through MTT assays while apoptosis was investigated using Annexin V-FITC/PI kit and flow cytometry. Enzyme-linked immunosorbent assay (ELISA) was used to detect IL-6, IL-8, and TNF-α cytokines expressions. AKT/mTOR and autophagy proteins expressions were investigated through western blot and immunofluorescence. The results indicated significantly inhibited cell viability following ACHN tumor cells treatments with curcumin alone, or with the various combinations, as compared to the control. Apoptosis was significantly increased following curcumin treatment, but was significantly reversed after treatment with curcumin+ 3-MA. Likewise, AKT/mTOR proteins expression were significantly reduced while the autophagy-related proteins were significantly elevated following curcumin treatment. The tumor size, weight and volumes were also significantly suppressed following treatment with curcumin. In conclusion, the investigation demonstrated that curcumin suppressed ACHN cell viability, induced apoptosis and autophagy, through the suppression of AKT/mTOR pathway. Use of curcumin to target AKT/mTOR pathway could be an effective treatment alternative for renal cell carcinoma.
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Affiliation(s)
- Xuelian Gong
- Department of Pharmacy, Qishan Hospital, Yantai, China
| | - Ling Jiang
- Department of Pharmacy, Qishan Hospital, Yantai, China
| | - Wei Li
- Department of Pharmacy, Qishan Hospital, Yantai, China
| | - Qingbin Liang
- Department of Emergency, Qingdao Women and Children’s Hospital, Yantai, Shandong, China
| | - Zhen Li
- Yantai Yuhuangding Hospital, Yantai, Shandong, China
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15
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Xue L, Tao Y, Yuan Y, Qu W, Wang W. Curcumin suppresses renal carcinoma tumorigenesis by regulating circ-FNDC3B/miR-138-5p/IGF2 axis. Anticancer Drugs 2021; 32:734-744. [PMID: 34001703 DOI: 10.1097/cad.0000000000001063] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Curcumin has a vital role in the development of renal carcinoma. Nevertheless, the mechanism of curcumin in renal carcinoma tumorigenesis remains largely unknown. Thirty renal carcinoma patients were recruited. Renal carcinoma cell lines CAKI-1 and ACHN were exposed to curcumin. The levels of circular RNA fibronectin type III domain-containing protein 3B (circ-FNDC3B), microRNA (miR)-138-5p and insulin-like growth factor 2 (IGF2) were detected via quantitative reverse transcription PCR or western blot. Cell proliferation and apoptosis were investigated via 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide, colony formation analysis, flow cytometry and western blot. Target association between miR-138-5p and circ-FNDC3B or IGF2 was analyzed via dual-luciferase reporter analysis. The function of curcumin in vivo was assessed via a xenograft model. circ-FNDC3B level was enhanced and miR-138-5p abundance was declined in renal carcinoma tissues and cells. Curcumin restrained renal carcinoma cell proliferation and promoted apoptosis. circ-FNDC3B overexpression or miR-138-5p knockdown weakened the influence of curcumin. circ-FNDC3B knockdown hindered cell proliferation and promoted apoptosis by increasing miR-138-5p. IGF2 was targeted via miR-138-5p and positively regulated via circ-FNDC3B. Curcumin decreased xenograft tumor growth via reducing circ-FNDC3B in vivo. Curcumin suppressed renal carcinoma tumorigenesis in vitro and in vivo via regulating circ-FNDC3B/miR-138-5p/IGF2 axis, proposing new insight into renal carcinoma tumorigenesis.
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Affiliation(s)
- Li Xue
- Departments of Nephrology
| | | | - Yanjuan Yuan
- Urology, Nantong Hospital of Traditional Chinese Medicine, Nantong, China
| | - Wei Qu
- Departments of Nephrology
| | - Wei Wang
- Urology, Nantong Hospital of Traditional Chinese Medicine, Nantong, China
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16
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Almatroodi SA, Syed MA, Rahmani AH. Potential Therapeutic Targets of Curcumin, Most Abundant Active Compound of Turmeric Spice: Role in the Management of Various Types of Cancer. Recent Pat Anticancer Drug Discov 2021; 16:3-29. [PMID: 33143616 DOI: 10.2174/1574892815999201102214602] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Revised: 08/28/2020] [Accepted: 08/31/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND Curcumin, an active compound of turmeric spice, is one of the most-studied natural compounds and has been widely recognized as a chemopreventive agent. Several molecular mechanisms have proven that curcumin and its analogs play a role in cancer prevention through modulating various cell signaling pathways as well as in the inhibition of the carcinogenesis process. OBJECTIVE To study the potential role of curcumin in the management of various types of cancer through modulating cell signalling molecules based on available literature and recent patents. METHODS A wide-ranging literature survey was performed based on Scopus, PubMed, PubMed Central, and Google scholar for the implication of curcumin in cancer management, along with a special emphasis on human clinical trials. Moreover, patents were searched through www.google.com/patents, www.freepatentsonline.com, and www.freshpatents.com. RESULT Recent studies based on cancer cells have proven that curcumin has potential effects against cancer cells as it prevents the growth of cancer and acts as a cancer therapeutic agent. Besides, curcumin exerted anti-cancer effects by inducing apoptosis, activating tumor suppressor genes, cell cycle arrest, inhibiting tumor angiogenesis, initiation, promotion, and progression stages of tumor. It was established that co-treatment of curcumin and anti-cancer drugs could induce apoptosis and also play a significant role in the suppression of the invasion and metastasis of cancer cells. CONCLUSION Accumulating evidences suggest that curcumin has the potential to inhibit cancer growth, induce apoptosis, and modulate various cell signaling pathway molecules. Well-designed clinical trials of curcumin based on human subjects are still needed to establish the bioavailability, mechanism of action, efficacy, and safe dose in the management of various cancers.
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Affiliation(s)
- Saleh A Almatroodi
- Department of Medical Laboratories, College of Applied Medical Science, Qassim University, Buraydah 52571, Saudi Arabia
| | - Mansoor Ali Syed
- Department of Biotechnology, Faculty of Natural Sciences, Translational Research Lab, Jamia Millia Islamia, New Delhi 110025, India
| | - Arshad Husain Rahmani
- Department of Medical Laboratories, College of Applied Medical Science, Qassim University, Buraydah 52571, Saudi Arabia
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17
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Sadoughi F, Maleki Dana P, Asemi Z, Yousefi B. Targeting microRNAs by curcumin: implication for cancer therapy. Crit Rev Food Sci Nutr 2021; 62:7718-7729. [PMID: 33905266 DOI: 10.1080/10408398.2021.1916876] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
In spite of all the investigations in the past 20 years that established a great body of knowledge in cancer therapy, utilizing some elderly methods such as plant compound administration might still be useful. Curcumin is a bioactive polyphenol, which has many anticancer properties but its capability in modulating miRNA expression has opened new doors in the field of cancer-targeted therapy. MiRNAs are a class of small noncoding RNAs that are able to regulate gene expression and signaling. In addition, some other effects of these RNAs such as modulating cell differentiation and regulation of cell cycle have made miRNAs great candidates for personalized cancer treatment. In this review, we try to find some answers to the questions on how curcumin exerts its impacts on cancer hallmarks through miRNAs and whether chemotherapy can be replaced by this beneficial plant compound.
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Affiliation(s)
- Fatemeh Sadoughi
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Islamic Republic of Iran
| | - Parisa Maleki Dana
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Islamic Republic of Iran
| | - Zatollah Asemi
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Islamic Republic of Iran
| | - Bahman Yousefi
- Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Department of Biochemistry, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
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18
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Wang D, Yu D, Liu X, Wang Q, Chen X, Hu X, Wang Q, Jin C, Wen L, Zhang L. Targeting laryngeal cancer cells with 5-fluorouracil and curcumin using mesoporous silica nanoparticles. Technol Cancer Res Treat 2020; 19:1533033820962114. [PMID: 33267716 PMCID: PMC7720313 DOI: 10.1177/1533033820962114] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Objective: To explore the inhibitory and synergistic effects of 5-fluorouracil and curcumin on Hep-2 laryngeal cancer cells and clarify the effect of mesoporous silica nanoparticles as drug carriers. Methods: The inhibitory effects of 5-fluorouracil and curcumin on Hep-2 cells were detected using the CCK-8 assay. CompuSyn was used to calculate the synergistic effect of the 2 drugs. Flow cytometry was used to detect apoptosis and cell cycle arrest induced by 5-fluorouracil and curcumin. The drugs were loaded into mesoporous nanoparticles. Western blotting was used to detect the expression of related proteins after treatment. The growth of subcutaneous tumors in BALB/c nude after the intraperitoneal injection with drug-loaded mesoporous silica nanoparticles was recorded. Results: 5-Fluorouracil and curcumin synergistically induced apoptosis and cell cycle arrest in Hep-2 cells. Mesoporous silica nanoparticles as drug carriers enhanced the therapeutic effects of 5-fluorouracil and curcumin. Conclusions: Mesoporous silica nanoparticles are expected to be effective drug carriers that enhance the synergistic effects of 5-fluorouracil and curcumin on laryngeal cancer.
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Affiliation(s)
- Ding Wang
- Department of Otolaryngology, Head and Neck Surgery, the Second Hospital, 12510Jilin University, Changchun, Jilin, People's Republic of China.,Department of Pathophysiology, College of Basic Medical Science, 12510Jilin University, Changchun, Jilin, People's Republic of China
| | - Dan Yu
- Department of Otolaryngology, Head and Neck Surgery, the Second Hospital, 12510Jilin University, Changchun, Jilin, People's Republic of China
| | - Xueshibojie Liu
- Department of Otolaryngology, Head and Neck Surgery, the Second Hospital, 12510Jilin University, Changchun, Jilin, People's Republic of China
| | - Qian Wang
- Department of Pathophysiology, College of Basic Medical Science, 12510Jilin University, Changchun, Jilin, People's Republic of China
| | - Xuyang Chen
- Department of Pathophysiology, College of Basic Medical Science, 12510Jilin University, Changchun, Jilin, People's Republic of China
| | - Xindan Hu
- Department of Pathophysiology, College of Basic Medical Science, 12510Jilin University, Changchun, Jilin, People's Republic of China
| | - Qiong Wang
- Department of Pathophysiology, College of Basic Medical Science, 12510Jilin University, Changchun, Jilin, People's Republic of China
| | - Chunshun Jin
- Department of Otolaryngology, Head and Neck Surgery, the Second Hospital, 12510Jilin University, Changchun, Jilin, People's Republic of China
| | - Lianji Wen
- Department of Otolaryngology, Head and Neck Surgery, the Second Hospital, 12510Jilin University, Changchun, Jilin, People's Republic of China
| | - Ling Zhang
- Department of Pathophysiology, College of Basic Medical Science, 12510Jilin University, Changchun, Jilin, People's Republic of China
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19
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Zepeda-Quiróz I, Sánchez-Barrera H, Colín-Val Z, Robledo-Cadena DX, Rodríguez-Enríquez S, López-Marure R. Curcumin promotes oxidative stress, apoptosis and autophagy in H9c2 rat cardiomyoblasts. Mol Cell Toxicol 2020. [DOI: 10.1007/s13273-020-00101-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
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20
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Spray-drying microencapsulation of curcumin nanocomplexes with soy protein isolate: Encapsulation, water dispersion, bioaccessibility and bioactivities of curcumin. Food Hydrocoll 2020. [DOI: 10.1016/j.foodhyd.2020.105821] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
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21
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Tamaddoni A, Mohammadi E, Sedaghat F, Qujeq D, As'Habi A. The anticancer effects of curcumin via targeting the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway. Pharmacol Res 2020; 156:104798. [PMID: 32278045 DOI: 10.1016/j.phrs.2020.104798] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2019] [Revised: 03/26/2020] [Accepted: 03/29/2020] [Indexed: 01/19/2023]
Abstract
The mammalian target of rapamycin (mTOR) is a protein kinase that has been considered as a key regulator of a large number of cellular processes, including cell growth, proliferation, differentiation, survival, and motility. Overactivation of mTOR (especially mTORC1) signaling is related to oncogenic cellular processes. Therefore targeting mTORC1 signaling is a new promising strategy in cancer therapy. In this regard, various studies have shown that curcumin, a polyphenol produced from the turmeric rhizome, has anti-inflammatory, antioxidant and anticancer properties. Curcumin may exert its anticancer function, at least in part, by suppressing mTOR-mediated signaling pathway in tumor cells. However, the exact underlying mechanisms by which curcumin blocks the mTORC1 signaling remain unclear. According to literature, curcumin inhibits insulin-like growth factor 1 (IGF-1)/phosphoinositide 3-kinase (PI3K)/Akt/mTORC1 pathway which leads to apoptosis and cell cycle arrest via suppression of erythroblastosis virus transcription factor 2 and murine double minute 2 oncoprotein. In addition, activation of unc-51-like kinase 1 by curcumin, as a downstream target of IGF-1/PI3K/Akt/mTORC1 axis, enhances autophagy. Curcumin induces AMP-activated protein kinase, a negative regulator of mTORC1, via inhibition of F0F1-ATPase. Interestingly, curcumin suppresses IκB kinase β, the upstream kinase in mTORC1 pathway. Moreover, evidence revealed that curcumin downregulates the E3-ubiquitin ligases NEDD4, neural precursor cell-expressed developmentally downregulated 4. NEDD4 is frequently overexpressed in a wide range of cancers and degrades the phosphatase and tensin homolog, which is a negative regulator of mTORC1. Finally another suggested mechanism is suppression of MAOA/mTORC1/hypoxia-inducible factor 1α signaling pathway by curcumin.
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Affiliation(s)
- Ahmad Tamaddoni
- Non-Communicable Pediatric Diseases Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Elahe Mohammadi
- Department of Nutrition, Khalkhal University of Medical Sciences, Khalkhal, Iran.
| | - Fatemeh Sedaghat
- Department of Basic Medical Sciences, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Durdi Qujeq
- Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Atefeh As'Habi
- Food Safety Research Center (Salt), Semnan University of Medical Sciences, Semnan, Iran; Department of Nutrition, School of Nutrition and Food Sciences, Semnan University of Medical Sciences, Semnan, Iran
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22
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D'Angelo S, Scafuro M, Meccariello R. BPA and Nutraceuticals, Simultaneous Effects on Endocrine Functions. Endocr Metab Immune Disord Drug Targets 2020; 19:594-604. [PMID: 30621569 PMCID: PMC7360909 DOI: 10.2174/1871530319666190101120119] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2018] [Revised: 10/02/2018] [Accepted: 12/21/2018] [Indexed: 12/20/2022]
Abstract
Background Bisphenol A (BPA) is worldwide diffused as a monomer of epoxy resins and polycarbonate plastics and has recognized activity as Endocrine Disruptor (ED). It is capable to interfere or compete with endogenous hormones in many physiological activities thus having adverse outcomes on health. Diet highly affects health status and in addition to macronutrients, provides a large number of substances with recognized pro-heath activity, and thus called nutraceuticals. Objective This mini-review aims at summarizing the possible opposite and simultaneous effects of BPA and nutraceuticals on endocrine functions. The possibility that diet may represent the first instrument to preserve health status against BPA damages has been discussed. Methods The screening of recent literature in the field has been carried out. Results The therapeutic and anti-oxidant properties of many nutraceuticals may reverse the adverse health effects of BPA. Conclusion In vitro and in vivo studies provided evidence that nutraceuticals can preserve the health. Thus, the use of nutraceuticals can be considered a support for clinical treatment. In conclusion, dietary remediation may represent a successful therapeutic approach to maintain and preserve health against BPA damage.
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Affiliation(s)
- Stefania D'Angelo
- Dipartimento di Scienze Motorie e del Benessere, Universita di Napoli Parthenope, Napoli, Italy
| | - Marika Scafuro
- Dipartimento di Medicina Sperimentale sez "F. Bottazzi", Universita degli Studi della Campania "Luigi Vanvitelli", Napoli, Italy
| | - Rosaria Meccariello
- Dipartimento di Scienze Motorie e del Benessere, Universita di Napoli Parthenope, Napoli, Italy
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23
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Zhou Y, Yu F, Luo B, Luo H, Liu C. Cytrarabine (Ara-c) promotes cell apoptosis by inhibiting the phosphorylation of Protein Kinase B (AKT/PKB). Process Biochem 2019. [DOI: 10.1016/j.procbio.2019.04.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
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24
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Wang M, Jiang S, Zhou L, Yu F, Ding H, Li P, Zhou M, Wang K. Potential Mechanisms of Action of Curcumin for Cancer Prevention: Focus on Cellular Signaling Pathways and miRNAs. Int J Biol Sci 2019; 15:1200-1214. [PMID: 31223280 PMCID: PMC6567807 DOI: 10.7150/ijbs.33710] [Citation(s) in RCA: 108] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2019] [Accepted: 04/10/2019] [Indexed: 12/15/2022] Open
Abstract
Despite significant progressions in treatment modalities over the last decade, either cancer incidence or mortality is continuously on the rise throughout the world. Current anticancer agents display limited efficacy, accompanied by severe side effects. In order to improve therapeutic outcomes in patients with cancer, it is crucial to identify novel, highly efficacious pharmacological agents. Curcumin, a hydrophobic polyphenol extracted from turmeric, has gained increasing attention due to its powerful anticancer properties. Curcumin can inhibit the growth, invasion and metastasis of various cancers. The anticancer mechanisms of curcumin have been extensively studied. The anticancer effects of curcumin are mainly mediated through its regulation of multiple cellular signaling pathways, including Wnt/β-catenin, PI3K/Akt, JAK/STAT, MAPK, p53 and NF-ĸB signaling pathways. Moreover, curcumin also orchestrates the expression and activity of oncogenic and tumor-suppressive miRNAs. In this review, we summarized the regulation of these signaling pathways by curcumin in different cancers. We also discussed the modulatory function of curcumin in the downregulation of oncogenic miRNAs and the upregulation of tumor-suppressive miRNAs. An in-depth understanding of the anticancer mechanisms of curcumin will be helpful for developing this promising compound as a therapeutic agent in clinical management of cancer.
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Affiliation(s)
- Man Wang
- Institute for Translational Medicine, Medical College of Qingdao University, Dengzhou Road 38, Qingdao 266021, China
| | - Shuai Jiang
- Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China
| | - Li Zhou
- Animal Biosafety Level III Laboratory at the Center for Animal Experiment, Wuhan University School of Medicine, Wuhan 430071, China
| | - Fei Yu
- Institute for Translational Medicine, Medical College of Qingdao University, Dengzhou Road 38, Qingdao 266021, China
| | - Han Ding
- Institute for Translational Medicine, Medical College of Qingdao University, Dengzhou Road 38, Qingdao 266021, China
| | - Peifeng Li
- Institute for Translational Medicine, Medical College of Qingdao University, Dengzhou Road 38, Qingdao 266021, China
| | - Meng Zhou
- Department of Dermatology, Qilu Hospital of Shandong University (Qingdao), Qingdao 266000, China
| | - Kun Wang
- Institute for Translational Medicine, Medical College of Qingdao University, Dengzhou Road 38, Qingdao 266021, China
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Rutz J, Maxeiner S, Juengel E, Bernd A, Kippenberger S, Zöller N, Chun FKH, Blaheta RA. Growth and Proliferation of Renal Cell Carcinoma Cells Is Blocked by Low Curcumin Concentrations Combined with Visible Light Irradiation. Int J Mol Sci 2019; 20:ijms20061464. [PMID: 30909499 PMCID: PMC6471746 DOI: 10.3390/ijms20061464] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2019] [Revised: 03/13/2019] [Accepted: 03/21/2019] [Indexed: 12/17/2022] Open
Abstract
The anti-cancer properties of curcumin in vitro have been documented. However, its clinical use is limited due to rapid metabolization. Since irradiation of curcumin has been found to increase its anti-cancer effect on several tumor types, this investigation was designed to determine whether irradiation with visible light may enhance the anti-tumor effects of low-dosed curcumin on renal cell carcinoma (RCC) cell growth and proliferation. A498, Caki1, and KTCTL-26 cells were incubated with curcumin (0.1–0.4 µg/mL) and irradiated with 1.65 J/cm2 visible light for 5 min. Controls were exposed to curcumin or light alone or remained untreated. Curcumin plus light, but not curcumin or light exposure alone altered growth, proliferation, and apoptosis of all three RCC tumor cell lines. Cells were arrested in the G0/G1 phase of the cell cycle. Phosphorylated (p) CDK1 and pCDK2, along with their counter-receptors Cyclin B and A decreased, whereas p27 increased. Akt-mTOR-signaling was suppressed, the pro-apoptotic protein Bcl-2 became elevated, and the anti-apoptotic protein Bax diminished. H3 acetylation was elevated when cells were treated with curcumin plus light, pointing to an epigenetic mechanism. The present findings substantiate the potential of combining low curcumin concentrations and light as a new therapeutic concept to increase the efficacy of curcumin in RCC.
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Affiliation(s)
- Jochen Rutz
- Department of Urology, Goethe-University, D-60590 Frankfurt am Main, Germany.
| | - Sebastian Maxeiner
- Department of Urology, Goethe-University, D-60590 Frankfurt am Main, Germany.
| | - Eva Juengel
- Department of Urology, Goethe-University, D-60590 Frankfurt am Main, Germany.
- Current address: Department of Urology and Pediatric Urology, University Medical Center Mainz, D-55131 Mainz, Germany.
| | - August Bernd
- Department of Dermatology, Venereology, and Allergology, Goethe-University, D-60590 Frankfurt am Main, Germany.
| | - Stefan Kippenberger
- Department of Dermatology, Venereology, and Allergology, Goethe-University, D-60590 Frankfurt am Main, Germany.
| | - Nadja Zöller
- Department of Dermatology, Venereology, and Allergology, Goethe-University, D-60590 Frankfurt am Main, Germany.
| | - Felix K-H Chun
- Department of Urology, Goethe-University, D-60590 Frankfurt am Main, Germany.
| | - Roman A Blaheta
- Department of Urology, Goethe-University, D-60590 Frankfurt am Main, Germany.
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26
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Sun Y, Liu L, Wang Y, He A, Hu H, Zhang J, Han M, Huang Y. Curcumin inhibits the proliferation and invasion of MG-63 cells through inactivation of the p-JAK2/p-STAT3 pathway. Onco Targets Ther 2019; 12:2011-2021. [PMID: 30936718 PMCID: PMC6421868 DOI: 10.2147/ott.s172909] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Purpose The aims of this study were to determine the effect of curcumin on osteosarcoma (OS) cells due to inactivation of the p-JAK2/p-STAT3 pathway and evaluate the prognostic value of this pathway in OS. Materials and methods We exposed a human OS cell line (MG-63) to different concentrations of curcumin. Then, we characterized the effects on MG-63 cells using assays (cell viability, colony formation, cell cycle, wound healing, invasion), flow cytometry, Western blot, immunohistochemical analyses, and tumor xenograft. Results The half-maximal inhibitory of curcumin for MG-63 cells at 24 hours was 27.6 µM. The number of colonies of MG-63 cells was decreased obviously upon curcumin (10 and 20 µM) treatment. We also found increased accumulation of MG-63 cells in the G2/M phase upon curcumin (10 and 20 µM) treatment. Apoptosis was increased in 10 and 20 µM curcumin-treated MG-63 cells. After incubation of physically wounded cells for 24 hours, the percentage wound width increased upon curcumin exposure. Curcumin obviously decreased the expression of pJAK-2 and pSTAT-3 in MG-63 cells in a dose-dependent manner. Curcumin dose-dependently inhibited the proliferation, migration, and invasion of MG-63 cells and induced arrest of the G0/G1 phase and apoptosis by inhibiting the p-JAK2/p-STAT3 pathway. The linear correlativity between expression of p-JAK2 and STAT3 was very prominent, and both were closely associated with lung metastasis. In vivo study suggested that curcumin suppressed tumor growth through JAK2/STAT3 signaling. Conclusion Curcumin-mediated inhibition of the proliferation and migration of MG-63 cells was associated with inactivation of JAK/STAT signaling.
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Affiliation(s)
- Yuanjue Sun
- Cancer Therapy and Research Center, Shandong Provincial Hospital, Shandong University, 250021, Shandong, People's Republic of China,
| | - Liguo Liu
- Department of General Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 200233 Shanghai, People's Republic of China
| | - Yaling Wang
- Department of Medical Oncology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 200233 Shanghai, People's Republic of China,
| | - Aina He
- Department of Medical Oncology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 200233 Shanghai, People's Republic of China,
| | - Haiyan Hu
- Department of Medical Oncology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 200233 Shanghai, People's Republic of China,
| | - Jianjun Zhang
- Department of Medical Oncology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 200233 Shanghai, People's Republic of China,
| | - Mingyong Han
- Cancer Therapy and Research Center, Shandong Provincial Hospital, Shandong University, 250021, Shandong, People's Republic of China,
| | - Yujing Huang
- Department of Medical Oncology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 200233 Shanghai, People's Republic of China,
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Li J, Feng D, Gao C, Zhang Y, Xu J, Wu M, Zhan X. Isoforms S and L of MRPL33 from alternative splicing have isoform‑specific roles in the chemoresponse to epirubicin in gastric cancer cells via the PI3K/AKT signaling pathway. Int J Oncol 2019; 54:1591-1600. [PMID: 30816492 PMCID: PMC6438423 DOI: 10.3892/ijo.2019.4728] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2018] [Accepted: 02/06/2019] [Indexed: 12/16/2022] Open
Abstract
Drug resistance is a major cause of cancer-associated mortality. Epirubicin-based chemotherapy initially benefits patients with metastatic or advanced gastric cancer; however, tumor recurrence can occur following several courses of treatment. Mitochondrial ribosomal protein L33 (MRPL33)-long (L) and MRPL33-short (S), isoforms of MRPL33 that arise from AS, have been reported to regulate cell growth and apoptosis in cancer; however, few studies have evaluated the roles of MRPL33-L and MRPL33-S in gastric cancer. In the present study, MRPL33-L was demonstrated to be significantly more abundant in gastric tumor tissues than the MRPL33-S isoform. MRPL33-S promoted chemosensitivity to epirubicin in gastric cancer as demonstrated by a chemoresponse assay; chemosensitivity was suppressed in response to MRPL33-L. Gene microarray analysis was performed to investigate the underlying mechanisms. Bioinformatic analysis revealed that overexpression of MRPL33-L and MRPL33-S served critical roles in transcription, signal transduction and apoptosis. In particular, the phosphoinositide 3-kinase (PI3K)/AKT serine/threonine kinase (AKT) signaling pathway was markedly regulated. A total of 36 target genes, including PIK3 regulatory subunit α, AKT2, cAMP response element-binding protein (CREB) 1, forkhead box 3, glycogen synthase kinase 3β and mammalian target of rapamycin, which are involved in the PI3K/AKT signaling pathway, were selected for further investigation via protein-protein interaction network and Kyoto Encyclopedia of Genes and Genomes pathway analyses. Furthermore, western blot analysis indicated that MRPL33-S promoted the chemoresponse to epirubicin by deactivating PI3K/AKT/CREB signaling and inducing apoptosis, while MRPL33-L had the opposite effects. In conclusion, the results of the present study revealed that isoforms S and L of MRPL33, which arise from alternative splicing, exhibited opposing roles in the chemoresponse to epirubicin in gastric cancer via the PI3K/AKT signaling pathway. These findings may contribute to the development of potential therapeutic strategies for the resensitization of patients with gastric cancer to epirubicin treatment.
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Affiliation(s)
- Jie Li
- Department of Oncology, The Changhai Hospital, Shanghai 200433, P.R. China
| | - Dan Feng
- Department of Oncology, The Changhai Hospital, Shanghai 200433, P.R. China
| | - Cuixia Gao
- Department of Research and Development, The Shanghai Polaris Biology Technology, Shanghai 201203, P.R. China
| | - Yingyi Zhang
- Department of Oncology, The Changhai Hospital, Shanghai 200433, P.R. China
| | - Jing Xu
- Department of Oncology, The Changhai Hospital, Shanghai 200433, P.R. China
| | - Meihong Wu
- Department of Oncology, The Changhai Hospital, Shanghai 200433, P.R. China
| | - Xianbao Zhan
- Department of Oncology, The Changhai Hospital, Shanghai 200433, P.R. China
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Sun K, Jia Z, Duan R, Yan Z, Jin Z, Yan L, Li Q, Yang J. Long non-coding RNA XIST regulates miR-106b-5p/P21 axis to suppress tumor progression in renal cell carcinoma. Biochem Biophys Res Commun 2019; 510:416-420. [PMID: 30717973 DOI: 10.1016/j.bbrc.2019.01.116] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2019] [Accepted: 01/26/2019] [Indexed: 01/01/2023]
Abstract
Long non-coding RNAs (lncRNAs) have been demonstrated to exert important roles in cancer development and progression. The biological function of lncRNA X-inactive specific transcript (XIST) in the development of renal cell carcinoma (RCC) and the underlying mechanisms are still largely unknown. In this study, we found that XIST was down-regulated in RCC tissues and cells. Overexpression of XIST significantly suppressed cell proliferation and induced cell G0/G1 arrest in vitro and inhibited tumor growth in vivo. We further found that XIST could directly interact with miR-106b-5p and increase the expression of P21. Thus, XIST positively regulated the expression of P21 through sponging miR-106b-5p, and played a tumor suppressor role in RCC. Moreover, we found that curcumin could regulate XIST/miR-106b-5p/P21 axis in RCC cells. Our study exhibits the role of XIST as a miRNA sponge in RCC and supports the potential application of XIST in RCC therapy.
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Affiliation(s)
- Ke Sun
- Department of Urology, The First Affiliated Hospital, Zhengzhou University, No 1 Jianshe East Rd., Zhengzhou, 450052, People's Republic of China; Urological Institute of Henan, Zhengzhou, 450052, Henan Province, People's Republic of China
| | - Zhankui Jia
- Department of Urology, The First Affiliated Hospital, Zhengzhou University, No 1 Jianshe East Rd., Zhengzhou, 450052, People's Republic of China
| | - Ranran Duan
- Department of Neurology, The First Affiliated Hospital, Zhengzhou University, No 1 Jianshe East Rd., Zhengzhou, 450052, People's Republic of China
| | - Zechen Yan
- Department of Urology, The First Affiliated Hospital, Zhengzhou University, No 1 Jianshe East Rd., Zhengzhou, 450052, People's Republic of China; Urological Institute of Henan, Zhengzhou, 450052, Henan Province, People's Republic of China
| | - Zhibo Jin
- Department of Urology, The First Affiliated Hospital, Zhengzhou University, No 1 Jianshe East Rd., Zhengzhou, 450052, People's Republic of China; Urological Institute of Henan, Zhengzhou, 450052, Henan Province, People's Republic of China
| | - Liang Yan
- Department of Urology, The First Affiliated Hospital, Zhengzhou University, No 1 Jianshe East Rd., Zhengzhou, 450052, People's Republic of China; Urological Institute of Henan, Zhengzhou, 450052, Henan Province, People's Republic of China
| | - Qi Li
- Department of Urology, The First Affiliated Hospital, Zhengzhou University, No 1 Jianshe East Rd., Zhengzhou, 450052, People's Republic of China; Urological Institute of Henan, Zhengzhou, 450052, Henan Province, People's Republic of China
| | - Jinjian Yang
- Department of Urology, The First Affiliated Hospital, Zhengzhou University, No 1 Jianshe East Rd., Zhengzhou, 450052, People's Republic of China; Urological Institute of Henan, Zhengzhou, 450052, Henan Province, People's Republic of China.
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Liu Y, Wang X, Zeng S, Zhang X, Zhao J, Zhang X, Chen X, Yang W, Yang Y, Dong Z, Zhu J, Xu X, Tian F. The natural polyphenol curcumin induces apoptosis by suppressing STAT3 signaling in esophageal squamous cell carcinoma. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH : CR 2018; 37:303. [PMID: 30518397 PMCID: PMC6280482 DOI: 10.1186/s13046-018-0959-0] [Citation(s) in RCA: 69] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/28/2018] [Accepted: 11/13/2018] [Indexed: 12/12/2022]
Abstract
Background We and others have previously shown that the STAT3 signaling pathway is activated in some esophageal squamous cell carcinoma (ESCC) cells and is required for the survival and growth of these primary ESCC-derived xenografts. It has also been shown that the natural polyphenol curcumin is an effective anti-tumor agent. Methods Luciferase assay and immunoblotting were performed to examine whether curcumin suppressed STAT3 signaling. CCK-8 assay and xenografts were utilized for analyzing ESCC cell growth in culture and mice. Soft agar assay was carried out to determine the colony formation ability of ESCC cells in the presence or absence of curcumin. Cell death and cell cycle were assessed by In CELL Analyzer 2000. Immunohistochemistry and TUNEL assay were used for detecting apoptosis in ESCC tisuses. Molecular docking was performed to evaluate the interaction of curcumin with JAK2. JAK2 activity was assessed using an in vitro cell-free system. HE staining was used to evaluate the ESCC tissues. Results The natural polyphenol curcumin inhibited STAT3 phosphorylation rapidly and blocked STAT3-mediated signaling in ESCC cells. It also induced growth arrest and apoptosis in cultured ESCC cells, which were attenuated by enforced expression of STAT3. Furthermore, curcumin preferentially blocked the growth of primary ESCC-derived xenografts that harbored activated STAT3. Conclusions Curcumin is able to exert anti-tumor action through inhibiting the STAT3 signaling pathway. Giving its wide use in traditional medicines with low toxicity and few adverse reactions, it is conceivable that curcumin might be further explored as a unique STAT3 inhibitor for anti-cancer therapies.
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Affiliation(s)
- Ying Liu
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, People's Republic of China.,Henan Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou, Henan, 450001, People's Republic of China.,Clinical Research Center, People's Hospital of Zhengzhou, Zhengzhou, Henan, 450001, People's Republic of China
| | - Xinhua Wang
- Department of Histology and Embryology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, People's Republic of China
| | - Shuang Zeng
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, People's Republic of China.,Henan Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou, Henan, 450001, People's Republic of China
| | - Xiane Zhang
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, People's Republic of China.,Henan Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou, Henan, 450001, People's Republic of China
| | - Jimin Zhao
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, People's Republic of China.,Henan Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou, Henan, 450001, People's Republic of China
| | - Xiaoyan Zhang
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, People's Republic of China.,Henan Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou, Henan, 450001, People's Republic of China
| | - Xinhuan Chen
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, People's Republic of China.,Henan Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou, Henan, 450001, People's Republic of China
| | - Wanjing Yang
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, People's Republic of China.,Henan Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou, Henan, 450001, People's Republic of China
| | - Yili Yang
- Suzhou Institute of Systems Medicine, Center for Systems Medicine, Chinese Academy of Medical Sciences, Suzhou, Jiangsu, 215123, People's Republic of China
| | - Ziming Dong
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, People's Republic of China.,Henan Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou, Henan, 450001, People's Republic of China
| | - Jingyu Zhu
- School of Medicine and Pharmaceutics, Jiangnan University, Wuxi, Jiangsu, 214000, People's Republic of China
| | - Xin Xu
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, People's Republic of China. .,Suzhou Institute of Systems Medicine, Center for Systems Medicine, Chinese Academy of Medical Sciences, Suzhou, Jiangsu, 215123, People's Republic of China.
| | - Fang Tian
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, People's Republic of China. .,Henan Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou, Henan, 450001, People's Republic of China.
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30
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Zhu X, Zhu R. Curcumin suppresses the progression of laryngeal squamous cell carcinoma through the upregulation of miR-145 and inhibition of the PI3K/Akt/mTOR pathway. Onco Targets Ther 2018; 11:3521-3531. [PMID: 29950857 PMCID: PMC6016259 DOI: 10.2147/ott.s159236] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Background Curcumin is a polyphenol extracted from the rhizomes of Curcuma longa with extensive biological and pharmacological effects. The present study aimed to investigate the mechanisms of curcumin in laryngeal squamous cell carcinoma (LSCC). Methods Quantitative real-time reverse transcriptase-polymerase chain reaction was performed to detect the expressions of miR-145 in LSCC tissues and cells. The effects of miR-145 and curcumin on cell proliferation, apoptosis, cell cycle, migration and invasion were explored by MTT assay, flow cytometry analysis, Transwell migration and invasion assay, respectively. The effects of miR-145 combined with curcumin on the phosphoinositol 1,3 kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway were detected by Western blot analysis. Results miR-145 was significantly downregulated in LSCC tissues and cells. Curcumin administration upregulated miR-145 expression in LSCC cells in a dose-dependent manner. miR-145 overexpression and curcumin treatment both markedly suppressed cell proliferation, migration and invasion and induced cell cycle arrest and apoptosis in LSCC cells. Moreover, curcumin treatment reversed the enhanced effects on cell viability, migration and invasion and the inhibitory effects on apoptosis conferred by anti-miR-145 in LSCC cells. Curcumin treatment dramatically aggravated miR-145-induced inhibition of the PI3K/Akt/mTOR pathway and reversed anti-miR-145-mediated activation of the PI3K/Akt/mTOR pathway in LSCC cells. Conclusion Curcumin suppressed LSCC progression through the upregulation of miR-145 and inhibition of the PI3K/Akt/mTOR pathway.
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Affiliation(s)
- Xiaofeng Zhu
- Department of Otorhinolaryngology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450000, People's Republic of China
| | - Ronghua Zhu
- Department of Otorhinolaryngology, Jinan Central Hospital Affiliated to Shandong University, Jinan 250013, People's Republic of China
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Siddiqui FA, Prakasam G, Chattopadhyay S, Rehman AU, Padder RA, Ansari MA, Irshad R, Mangalhara K, Bamezai RNK, Husain M, Ali SM, Iqbal MA. Curcumin decreases Warburg effect in cancer cells by down-regulating pyruvate kinase M2 via mTOR-HIF1α inhibition. Sci Rep 2018; 8:8323. [PMID: 29844464 PMCID: PMC5974195 DOI: 10.1038/s41598-018-25524-3] [Citation(s) in RCA: 94] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2017] [Accepted: 04/18/2018] [Indexed: 12/21/2022] Open
Abstract
Warburg effect is an emerging hallmark of cancer cells with pyruvate kinase M2 (PKM2) as its key regulator. Curcumin is an extensively-studied anti-cancer compound, however, its role in affecting cancer metabolism remains poorly understood. Herein, we show that curcumin inhibits glucose uptake and lactate production (Warburg effect) in a variety of cancer cell lines by down-regulating PKM2 expression, via inhibition of mTOR-HIF1α axis. Stable PKM2 silencing revealed that PKM2 is required for Warburg effect and proliferation of cancer cells. PKM2 over-expression abrogated the effects of curcumin, demonstrating that inhibition of Warburg effect by curcumin is PKM2-mediated. High PKM2 expression correlated strongly with poor overall survival in cancer, suggesting the requirement of PKM2 in cancer progression. The study unravels novel PKM2-mediated inhibitory effect of curcumin on metabolic capacities of cancer cells. To the best of our knowledge, this is the first study linking curcumin with PKM2-driven cancer glycolysis, thus, providing new perspectives into the mechanism of its anticancer activity.
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Affiliation(s)
- Farid Ahmad Siddiqui
- Department of Biotechnology, Faculty of Natural Sciences, Jamia Millia Islamia (A Central University), Jamia Nagar, New Delhi, 110025, India
| | - Gopinath Prakasam
- School of Life Sciences, Jawaharlal Nehru University, New Mehrauli Road, New Delhi, 110067, India
| | - Shilpi Chattopadhyay
- Department of Toxicology, School of Chemical and Life Sciences, Jamia Hamdard (Deemed University), New Delhi, 110062, India
| | - Asad Ur Rehman
- Department of Biotechnology, Faculty of Natural Sciences, Jamia Millia Islamia (A Central University), Jamia Nagar, New Delhi, 110025, India
- Department of Biosciences, Faculty of Natural Sciences, Jamia Millia Islamia (A Central University), Jamia Nagar, New Delhi, 110025, India
| | - Rayees Ahmad Padder
- Department of Biotechnology, Faculty of Natural Sciences, Jamia Millia Islamia (A Central University), Jamia Nagar, New Delhi, 110025, India
| | - Mohammad Afaque Ansari
- Department of Biotechnology, Faculty of Natural Sciences, Jamia Millia Islamia (A Central University), Jamia Nagar, New Delhi, 110025, India
| | - Rasha Irshad
- Department of Biotechnology, Faculty of Natural Sciences, Jamia Millia Islamia (A Central University), Jamia Nagar, New Delhi, 110025, India
| | - Kailash Mangalhara
- School of Life Sciences, Jawaharlal Nehru University, New Mehrauli Road, New Delhi, 110067, India
| | - Rameshwar N K Bamezai
- School of Life Sciences, Jawaharlal Nehru University, New Mehrauli Road, New Delhi, 110067, India
| | - Mohammad Husain
- Department of Biotechnology, Faculty of Natural Sciences, Jamia Millia Islamia (A Central University), Jamia Nagar, New Delhi, 110025, India
| | - Syed Mansoor Ali
- Department of Biotechnology, Faculty of Natural Sciences, Jamia Millia Islamia (A Central University), Jamia Nagar, New Delhi, 110025, India
| | - Mohammad Askandar Iqbal
- Department of Biotechnology, Faculty of Natural Sciences, Jamia Millia Islamia (A Central University), Jamia Nagar, New Delhi, 110025, India.
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Doello K, Ortiz R, Alvarez PJ, Melguizo C, Cabeza L, Prados J. Latest in Vitro and in Vivo Assay, Clinical Trials and Patents in Cancer Treatment using Curcumin: A Literature Review. Nutr Cancer 2018; 70:569-578. [DOI: 10.1080/01635581.2018.1464347] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Affiliation(s)
- Kevin Doello
- Medical Oncology Service, Virgen de las Nieves Hospital, Granada, Spain
- Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada, Spain
| | - Raúl Ortiz
- Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada, Spain
- Department of Health Science, University of Jaén, Jaén, Spain
| | - Pablo J. Alvarez
- Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada, Spain
| | - Consolación Melguizo
- Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada, Spain
- Department of Anatomy and Embryology, Faculty of Medicine, University of Granada, Granada, Spain
- Biosanitary Institute of Granada (ibs. GRANADA), SAS-Universidad de Granada, Granada, Spain
| | - Laura Cabeza
- Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada, Spain
- Department of Anatomy and Embryology, Faculty of Medicine, University of Granada, Granada, Spain
- Biosanitary Institute of Granada (ibs. GRANADA), SAS-Universidad de Granada, Granada, Spain
| | - José Prados
- Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada, Spain
- Department of Anatomy and Embryology, Faculty of Medicine, University of Granada, Granada, Spain
- Biosanitary Institute of Granada (ibs. GRANADA), SAS-Universidad de Granada, Granada, Spain
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The Role of Compounds Derived from Natural Supplement as Anticancer Agents in Renal Cell Carcinoma: A Review. Int J Mol Sci 2017; 19:ijms19010107. [PMID: 29301217 PMCID: PMC5796057 DOI: 10.3390/ijms19010107] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2017] [Revised: 12/24/2017] [Accepted: 12/28/2017] [Indexed: 12/24/2022] Open
Abstract
Renal Cell Carcinoma (RCC) is the most prominent kidney cancer derived from renal tubules and accounts for roughly 85% of all malignant kidney cancer. Every year, over 60,000 new cases are registered, and about 14,000 people die from RCC. The incidence of this has been increasing significantly in the U.S. and other countries. An increased understanding of molecular biology and the genomics of RCC has uncovered several signaling pathways involved in the progression of this cancer. Significant advances in the treatment of RCC have been reported from agents approved by the Food and Drug Administration (FDA) that target these pathways. These agents have become drugs of choice because they demonstrate clinical benefit and increased survival in patients with metastatic disease. However, the patients eventually relapse and develop resistance to these drugs. To improve outcomes and seek approaches for producing long-term durable remission, the search for more effective therapies and preventative strategies are warranted. Treatment of RCC using natural products is one of these strategies to reduce the incidence. However, recent studies have focused on these chemoprevention agents as anti-cancer therapies given they can inhibit tumor cell grow and lack the severe side effects common to synthetic compounds. This review elaborates on the current understanding of natural products and their mechanisms of action as anti-cancer agents. The present review will provide information for possible use of these products alone or in combination with chemotherapy for the prevention and treatment of RCC.
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Curcumin enhances the radiosensitivity of renal cancer cells by suppressing NF-κB signaling pathway. Biomed Pharmacother 2017; 94:974-981. [DOI: 10.1016/j.biopha.2017.07.148] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2017] [Revised: 07/18/2017] [Accepted: 07/30/2017] [Indexed: 01/06/2023] Open
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Wang J, Liu X, Yan C, Liu J, Wang S, Hong Y, Gu A, Zhao P. LEF1-AS1, a long-noncoding RNA, promotes malignancy in glioblastoma. Onco Targets Ther 2017; 10:4251-4260. [PMID: 28894380 PMCID: PMC5584905 DOI: 10.2147/ott.s130365] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVES The long-noncoding RNAs (lncRNAs) are identified as new crucial regulators of diverse cellular processes in glioblastoma (GBM) tissues. However, the expression pattern and biological function of lncRNAs remain largely unknown. Here, for the first time, the effects of lncRNA lymphoid enhancer-binding factor 1 antisense RNA 1 (LEF1-AS1) on GBM progression both in vitro and in vivo are investigated. MATERIALS AND METHODS Expression profiles of LEF1-AS1 in GBM specimens were investigated by bioinformatics analyses. LEF1-AS1 expression in GBM tissues was detected using a quantitative polymerase chain reaction. LEF1-AS1 expression was inhibited by transfecting the LEF1-AS1-specific small interfering RNAs (siRNAs) and stable cell lines established were inhibited by transfecting si-LEF1-AS1 viruses. The Cell Counting Kit-8, ethynyl deoxyuridine, and colony formation assay were used to examine proliferation function. The flow cytometry detected cell-cycle change and apoptosis. Migration effects were detected by a Transwell assay. The tumor xenografts and immunohistochemistry were performed to evaluate tumor growth in vivo. RESULTS In this study, LEF1-AS1 expression was found significantly upregulated in GBM specimens compared with normal tissues. The 5-year overall survival in GBM patients from The Cancer Genome Atlas with high expression of LEF1-AS1 was inferior to that with low expression. It was confirmed that expression of LEF1-AS1 was higher in GBM tissues than normal ones. Knockdown of LEF1-AS1 significantly inhibited the malignancy of GBM cells, including proliferation and invasion, and promoted cell apoptosis. The result of Western blot assays indicated that knockdown of LEF1-AS1-mediated tumor suppression in GBM cells may be via the reduction of ERK and Akt/mTOR signaling activities. Finally, the in vivo experiment also demonstrated that knockdown LEF1-AS1 inhibited the growth-promoting effect of LEF1-AS1 of U87 cells. CONCLUSION Our result indicated that lncRNA LEF1-AS1 acts as an oncogene in GBM and may be a pivotal target for this disease.
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Affiliation(s)
| | | | - Changsheng Yan
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing
| | - Jie Liu
- Xuzhou Maternity and Child Health Care Hospital, Xuzhou Medical University, Xuzhou
| | - Songtao Wang
- Department of Intensive Care Unit, Shanghai General Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai
| | | | - Aihua Gu
- State Key Laboratory of Reproductive Medicine, Institute of Toxicology
- Key Laboratory of Modern Toxicology, of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China
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Li H, Wu H, Zhang H, Li Y, Li S, Hou Q, Wu S, Yang SY. Identification of curcumin-inhibited extracellular matrix receptors in non-small cell lung cancer A549 cells by RNA sequencing. Tumour Biol 2017; 39:1010428317705334. [PMID: 28618934 DOI: 10.1177/1010428317705334] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Curcumin is a potent anti-cancer drug in several types of human cancers. Despite of several preclinical and clinical studies of curcumin, the precise mechanism of curcumin in cancer prevention has remained unclear. In our study, we for the first time investigated whole transcriptome alteration in A549 non-small cell lung cancer (NSCLC) cell lines after treatment with curcumin using RNA sequencing. We found that lots of genes and signaling pathways were significantly altered after curcumin treatment in A549 cells. With bioinformatics approaches (gene ontology, Kyoto Encyclopedia of Genes and Genomes, and STRING), we found that those curcumin altered genes were not only the genes that induce cell death but also those extracellular matrix receptors and mitogen-activated protein kinase signaling pathway genes which regulate cell migration and proliferation. Among those significantly altered genes, eight genes ( COL1A1, COL4A1, COL5A1, LAMA5, ITGA3, ITGA2B, DDIT3, and DUSP1) were further examined by quantitative reverse transcription polymerase chain reaction and western blot analysis in four non-small cell lung cancer cell lines. Both in cell lines and in mouse model, the extracellular matrix receptors including the integrin ( ITGA3 and ITGA2B), collagen ( COL5A1), and laminin ( LAMA5) were significantly inhibited by curcumin at messenger RNA and protein levels. Functional studies confirmed that curcumin not only induced A549 cell death but also repressed cell proliferation and migration by regulating extracellular matrix receptors. Collectively, our study suggests that curcumin may be used as a promising drug candidate for intervening lung cancer in future studies.
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Affiliation(s)
- Huiping Li
- 1 Department of Respiratory Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.,2 Department of Emergency Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Hongjin Wu
- 3 Cancer Research Institute, Hangzhou Cancer Hospital, Hangzhou, China
| | - Hongfang Zhang
- 3 Cancer Research Institute, Hangzhou Cancer Hospital, Hangzhou, China
| | - Ying Li
- 3 Cancer Research Institute, Hangzhou Cancer Hospital, Hangzhou, China
| | - Shuang Li
- 3 Cancer Research Institute, Hangzhou Cancer Hospital, Hangzhou, China
| | - Qiang Hou
- 3 Cancer Research Institute, Hangzhou Cancer Hospital, Hangzhou, China
| | - Shixiu Wu
- 3 Cancer Research Institute, Hangzhou Cancer Hospital, Hangzhou, China
| | - Shuan-Ying Yang
- 1 Department of Respiratory Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
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Curcumin Induces p53-Null Hepatoma Cell Line Hep3B Apoptosis through the AKT-PTEN-FOXO4 Pathway. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2017; 2017:4063865. [PMID: 28769986 PMCID: PMC5523542 DOI: 10.1155/2017/4063865] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/25/2017] [Accepted: 06/06/2017] [Indexed: 12/19/2022]
Abstract
Objective Curcumin (diferuloylmethane) is a yellow-colored polyphenol with antiproliferative and proapoptotic activities to various types of cancer cells. This study explored the mechanism by which curcumin induces p53-null hepatoma cell apoptosis. Results AKT, FOXO1, and FOXO3 proteins were downregulated after curcumin treatment. Conversely, PTEN was upregulated. Subcellular fractionations revealed that the FOXO4 protein translocated from cytosol into the nucleus after curcumin treatment. Overexpression of FOXO4 increases the sensitivity of Hep3B cells to curcumin. Knockdown of the FOXO4 gene by siRNA inhibits the proapoptotic effects of curcumin on Hep3B cell. Conclusions This study revealed the AKT/PTEN/FOXO4 pathway as a potential candidate of target for treatment of p53-null liver cancers.
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Li T, Mo H, Chen W, Li L, Xiao Y, Zhang J, Li X, Lu Y. Role of the PI3K-Akt Signaling Pathway in the Pathogenesis of Polycystic Ovary Syndrome. Reprod Sci 2016; 24:646-655. [PMID: 27613818 DOI: 10.1177/1933719116667606] [Citation(s) in RCA: 120] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
This review aimed to focus on the recent progress of the understanding of the role of phosphatidylinositol 3-kinase (PI3K) in polycystic ovary syndrome (PCOS). In recent years, it has been increasingly recognized that PI3K plays an important role in PCOS whose pathogenesis is unclear. However, research continues into revealing the details of how PI3Ks are involved in developing PCOS. Previous studies have shown that activation of the PI3K-protein kinase B (Akt) signaling pathway has important effects on insulin resistance and endometrial cancer. Knowledge of the action of PI3K in PCOS might provide valuable information to further validate the pathogenesis of PCOS and suggest new methods of treatment.
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Affiliation(s)
- Tiantian Li
- 1 Department of Obstetrics and Gynecology, Guangdong Women and Children Hospital, Guangzhou Medical University, Guangzhou, China
| | - Hui Mo
- 2 Laboratory of Chinese Medicine Quality Research, Macau University of Science and Technology, Macau, China
| | - Wenfeng Chen
- 1 Department of Obstetrics and Gynecology, Guangdong Women and Children Hospital, Guangzhou Medical University, Guangzhou, China
| | - Li Li
- 1 Department of Obstetrics and Gynecology, Guangdong Women and Children Hospital, Guangzhou Medical University, Guangzhou, China.,2 Laboratory of Chinese Medicine Quality Research, Macau University of Science and Technology, Macau, China
| | - Yao Xiao
- 2 Laboratory of Chinese Medicine Quality Research, Macau University of Science and Technology, Macau, China
| | - Jing Zhang
- 3 Guangzhou Family Planning Specialty Hospital, Guangzhou, China
| | - Xiaofang Li
- 1 Department of Obstetrics and Gynecology, Guangdong Women and Children Hospital, Guangzhou Medical University, Guangzhou, China
| | - Ying Lu
- 1 Department of Obstetrics and Gynecology, Guangdong Women and Children Hospital, Guangzhou Medical University, Guangzhou, China
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Niu T, Tian Y, Mei Z, Guo G. Inhibition of Autophagy Enhances Curcumin United light irradiation-induced Oxidative Stress and Tumor Growth Suppression in Human Melanoma Cells. Sci Rep 2016; 6:31383. [PMID: 27502897 PMCID: PMC4977547 DOI: 10.1038/srep31383] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2016] [Accepted: 07/20/2016] [Indexed: 12/15/2022] Open
Abstract
Malignant melanoma is the most aggressive form of skin carcinoma, which possesses fast propagating and highly invasive characteristics. Curcumin is a natural phenol compound that has various biological activities, such as anti-proliferative and apoptosis-accelerating impacts on tumor cells. Unfortunately, the therapeutical activities of Cur are severely hindered due to its extremely low bioavailability. In this study, a cooperative therapy of low concentration Cur combined with red united blue light irradiation was performed to inspect the synergistic effects on the apoptosis, proliferation and autophagy in human melanoma A375 cell. The results showed that red united blue light irradiation efficaciously synergized with Cur to trigger oxidative stress-mediated cell death, induce apoptosis and inhibit cell proliferation. Meanwhile, Western blotting revealed that combined disposure induced the formation of autophagosomes. Conversely, inhibition of the autophagy enhanced apoptosis, obstructed cell cycle arrest and induced reversible proliferation arrest to senescence. These findings suggest that Cur combined with red united blue light irradiation could generate photochemo-preventive effects via enhancing apoptosis and triggering autophagy, and pharmacological inhibition of autophagy convert reversible arrested cells to senescence, therefore reducing the possibility that damaged cells might escape programmed death.
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Affiliation(s)
- Tianhui Niu
- Aviation Medicine Research Laboratory, The General Hospital of the Air Force, Beijing, China
| | - Yan Tian
- Department of Dermatology, The General Hospital of the Air Force, Beijing, China
| | - Zhusong Mei
- Aviation Medicine Research Laboratory, The General Hospital of the Air Force, Beijing, China
| | - Guangjin Guo
- Aviation Medicine Research Laboratory, The General Hospital of the Air Force, Beijing, China
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