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Khan K, Anwar M, Badshah Y, Ashraf NM, Hamid A, Trembley JH, Shabbir M, Afsar T, Husain FM, Khan D, Razak S. Zapotin mitigates breast cancer progression by targeting PKCε mediated glycolytic pathway regulation. BMC Cancer 2025; 25:798. [PMID: 40296014 PMCID: PMC12039207 DOI: 10.1186/s12885-025-14202-z] [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: 01/28/2025] [Accepted: 04/22/2025] [Indexed: 04/30/2025] Open
Abstract
BACKGROUND The breast cancer recurrence and chemoresistance has increased over the years. A novel PKC, PKCε, may promote chemoresistance by causing hypoxia and cancer metabolic rewiring. A natural flavonoid, Zapotin, in colon cancer cells may modulate PKCε expression. Therefore, this study aimed to explore Zapotin impact on PKCε expression and the metabolic profile of breast cancer cells. METHODS Pharmacophore analysis of Zapotin was performed and molecular dynamics (MD) simulations were employed to study PKCε and Zapotin interaction stability. The effect of Zapotin treatment on PKCε expression and various aspects of cancer cell viability and metabolism was studied in MCF-7 and MDA-MB-231 breast cancer cell lines using real-time PCR, growth and death assays, and Gas Chromatography-Mass Spectrometry. RESULTS In silico analyses revealed good solubility and absorption of Zapotin with lower toxicity. Zapotin showed cancer cell-specific cytotoxicity (P < 0.0001). It's treatment also reduced breast cancer cell viability, colony formation, and migratory potential by targeting PKCε and associated HIF-1ɑ and VEGF signaling (P < 0.01). Zapotin also impacted PKCε-mediated metabolic signaling by targeting glycolytic pathways. CONCLUSION This study demonstrated the role of PKCε mediated HIF-1ɑ, VEGF, and glycolytic pathways in promoting breast carcinogenicity and demonstrated Zapotin as a potential treatment option for different types of breast tumors.
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Affiliation(s)
- Khushbukhat Khan
- Department of Biomedicine, Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), Islamabad, 44000, Pakistan
| | - Maryam Anwar
- Department of Biomedicine, Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), Islamabad, 44000, Pakistan
| | - Yasmin Badshah
- Department of Biomedicine, Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), Islamabad, 44000, Pakistan
| | - Naeem Mahmood Ashraf
- School of Biochemistry & Biotechnology, University of the Punjab, Lahore, Pakistan.
| | - Arslan Hamid
- LIMES Institute (AG-Netea), University of Bonn, Carl-Troll-Str. 31, 53115, Bonn, Germany
| | - Janeen H Trembley
- Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA
- Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA
- Minneapolis VA Health Care System Research Service, Minneapolis, MN, USA
| | - Maria Shabbir
- Department of Biomedicine, Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), Islamabad, 44000, Pakistan
| | - Tayyaba Afsar
- Department of Community Health Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Fohad Mabood Husain
- Department of Food Science and Nutrition, College of Food and Agriculture Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Dilawar Khan
- Department of Biomedicine, Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), Islamabad, 44000, Pakistan
| | - Suhail Razak
- Department of Community Health Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia.
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Niu C, Zhang J, Okolo PI, Daglilar E. Plant polyphenols in gastric cancer: Nature's healing touch. Semin Oncol 2025; 52:152333. [PMID: 40073717 DOI: 10.1053/j.seminoncol.2025.01.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2024] [Revised: 01/22/2025] [Accepted: 01/23/2025] [Indexed: 03/14/2025]
Abstract
Globally, gastric cancer ranks as the fifth most common cancer and is the third most common cause of malignancy-associated mortality. Although surgery is the primary treatment option for gastric cancer, adjuvant chemotherapy improves survival in patients following surgery. Proverbially, plant polyphenols have many beneficial health effects, including anticancer properties. Extensive studies have shown that plant polyphenols exhibit potential anticancer effects against gastric cancer in vitro and in vivo, as well as very few human studies. However, this topic has not yet been reviewed. The present review shows that the potential anticancer effect of plant polyphenols on gastric cancer was preliminarily attributed to their antiproliferative, antimetastatic, and antiangiogenic effects and modulations of apoptosis, autophagy, and intracellular reactive oxygen species. Moreover, conventional therapeutics combined with plant polyphenols make gastric cancer cells more sensitive to conventional therapy. We also discuss challenges and opportunities in translating plant polyphenol-based therapy to clinical applications. The content provided in this review is of interest to pharmacologists, ethnobotanists, and oncologists who are involved in phytomedicine.
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Affiliation(s)
- Chengu Niu
- Internal medicine residency program, Rochester General Hospital, Rochester, NY, USA.
| | - Jing Zhang
- Rainier Springs Behavioral Health Hospital, Vancouver, WA, USA
| | - Patrick I Okolo
- Division of Gastroenterology, Carillion Clinic, Roanoke, VA, USA
| | - Ebubekir Daglilar
- Division of Gastroenterology, Charleston Area Medical Center/CAMC Institute for Academic Medicine Program, Charleston, WV, USA
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Goyal H, Parwani S, Fatima K, Kaur J. Harnessing the power of Calculus bovis: Anti-cancer properties and Wnt pathway modulation in hepatocellular carcinoma. World J Gastroenterol 2024; 30:4496-4502. [DOI: 10.3748/wjg.v39.i41.4496] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Revised: 09/12/2024] [Accepted: 09/25/2024] [Indexed: 10/23/2024] Open
Abstract
In this manuscript, we comment on the article, which explores the anti-cancer effects of Calculus bovis (CB) in tumor biology. We highlight its potential, particularly in hepatocellular carcinoma (HCC), where it inhibits the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin pathways and induces apoptosis. CB contains compounds such as oleanolic acid and ursolic acid that target interleukin-6, mitogen-activated protein kinase 8, vascular endothelial growth factor, and caspase-3, offering anti-inflammatory and hepatoprotective benefits. The manuscript also discusses CB sativus (CBS), an artificial substitute, which has shown efficacy in reducing hepatic inflammation and oxidative stress in animal models. We emphasize the need for further research on the effects of CBS on the gut-liver axis and gut microbiota, and on targeting Wnt signaling and M2 tumor-associated macrophage as potential therapeutic strategies against HCC.
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Affiliation(s)
- Himanshi Goyal
- Department of Biochemistry, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Sachin Parwani
- Department of Biochemistry, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Kaneez Fatima
- Department of Biochemistry, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Jyotdeep Kaur
- Department of Biochemistry, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
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Goyal H, Parwani S, Fatima K, Kaur J. Harnessing the power of Calculus bovis: Anti-cancer properties and Wnt pathway modulation in hepatocellular carcinoma. World J Gastroenterol 2024; 30:4496-4502. [PMID: 39534422 PMCID: PMC11551676 DOI: 10.3748/wjg.v30.i41.4496] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Revised: 09/12/2024] [Accepted: 09/25/2024] [Indexed: 10/23/2024] Open
Abstract
In this manuscript, we comment on the article, which explores the anti-cancer effects of Calculus bovis (CB) in tumor biology. We highlight its potential, particularly in hepatocellular carcinoma (HCC), where it inhibits the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin pathways and induces apoptosis. CB contains compounds such as oleanolic acid and ursolic acid that target interleukin-6, mitogen-activated protein kinase 8, vascular endothelial growth factor, and caspase-3, offering anti-inflammatory and hepatoprotective benefits. The manuscript also discusses CB sativus (CBS), an artificial substitute, which has shown efficacy in reducing hepatic inflammation and oxidative stress in animal models. We emphasize the need for further research on the effects of CBS on the gut-liver axis and gut microbiota, and on targeting Wnt signaling and M2 tumor-associated macrophage as potential therapeutic strategies against HCC.
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Affiliation(s)
- Himanshi Goyal
- Department of Biochemistry, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Sachin Parwani
- Department of Biochemistry, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Kaneez Fatima
- Department of Biochemistry, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Jyotdeep Kaur
- Department of Biochemistry, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
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5
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He J, Qiu Z, Fan J, Xie X, Sheng Q, Sui X. Drug tolerant persister cell plasticity in cancer: A revolutionary strategy for more effective anticancer therapies. Signal Transduct Target Ther 2024; 9:209. [PMID: 39138145 PMCID: PMC11322379 DOI: 10.1038/s41392-024-01891-4] [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: 03/02/2024] [Revised: 05/21/2024] [Accepted: 06/03/2024] [Indexed: 08/15/2024] Open
Abstract
Non-genetic mechanisms have recently emerged as important drivers of anticancer drug resistance. Among these, the drug tolerant persister (DTP) cell phenotype is attracting more and more attention and giving a predominant non-genetic role in cancer therapy resistance. The DTP phenotype is characterized by a quiescent or slow-cell-cycle reversible state of the cancer cell subpopulation and inert specialization to stimuli, which tolerates anticancer drug exposure to some extent through the interaction of multiple underlying mechanisms and recovering growth and proliferation after drug withdrawal, ultimately leading to treatment resistance and cancer recurrence. Therefore, targeting DTP cells is anticipated to provide new treatment opportunities for cancer patients, although our current knowledge of these DTP cells in treatment resistance remains limited. In this review, we provide a comprehensive overview of the formation characteristics and underlying drug tolerant mechanisms of DTP cells, investigate the potential drugs for DTP (including preclinical drugs, novel use for old drugs, and natural products) based on different medicine models, and discuss the necessity and feasibility of anti-DTP therapy, related application forms, and future issues that will need to be addressed to advance this emerging field towards clinical applications. Nonetheless, understanding the novel functions of DTP cells may enable us to develop new more effective anticancer therapy and improve clinical outcomes for cancer patients.
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Affiliation(s)
- Jun He
- Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, China
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, China
| | - Zejing Qiu
- Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, China
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, China
| | - Jingjing Fan
- Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, China
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, China
| | - Xiaohong Xie
- Department of Breast Surgery, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
| | - Qinsong Sheng
- Department of Colorectal Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
| | - Xinbing Sui
- Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, China.
- Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, China.
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Zhang Y, Zhai W, Fan M, Wu J, Wang C. Salvianolic Acid B Significantly Suppresses the Migration of Melanoma Cells via Direct Interaction with β-Actin. Molecules 2024; 29:906. [PMID: 38398656 PMCID: PMC10892080 DOI: 10.3390/molecules29040906] [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: 01/03/2024] [Revised: 01/29/2024] [Accepted: 02/01/2024] [Indexed: 02/25/2024] Open
Abstract
Melanoma is the most aggressive and difficult to treat of all skin cancers. Despite advances in the treatment of melanoma, the prognosis for melanoma patients remains poor, and the recurrence rate remains high. There is substantial evidence that Chinese herbals effectively prevent and treat melanoma. The bioactive ingredient Salvianolic acid B (SAB) found in Salvia miltiorrhiza, a well-known Chinese herbal with various biological functions, exhibits inhibitory activity against various cancers. A375 and mouse B16 cell lines were used to evaluate the main targets and mechanisms of SAB in inhibiting melanoma migration. Online bioinformatics analysis, Western blotting, immunofluorescence, molecular fishing, dot blot, and molecular docking assays were carried out to clarify the potential molecular mechanism. We found that SAB prevents the migration and invasion of melanoma cells by inhibiting the epithelial-mesenchymal transition (EMT) process of melanoma cells. As well as interacting directly with the N-terminal domain of β-actin, SAB enhanced its compactness and stability, thereby inhibiting the migration of cells. Taken together, SAB could significantly suppress the migration of melanoma cells via direct binding with β-actin, suggesting that SAB could be a helpful supplement that may enhance chemotherapeutic outcomes and benefit melanoma patients.
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Affiliation(s)
| | | | | | - Jinjun Wu
- Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines of the Ministry of Education of the People’s Republic of China, Guangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China; (Y.Z.); (W.Z.); (M.F.)
| | - Caiyan Wang
- Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines of the Ministry of Education of the People’s Republic of China, Guangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China; (Y.Z.); (W.Z.); (M.F.)
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Huang J, Zhang J, Sun C, Yang R, Sheng M, Hu J, Kai G, Han B. Adjuvant role of Salvia miltiorrhiza bunge in cancer chemotherapy: A review of its bioactive components, health-promotion effect and mechanisms. JOURNAL OF ETHNOPHARMACOLOGY 2024; 318:117022. [PMID: 37572929 DOI: 10.1016/j.jep.2023.117022] [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: 06/15/2023] [Revised: 07/28/2023] [Accepted: 08/08/2023] [Indexed: 08/14/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Chemotherapy is a common cancer treatment strategy. However, its effectiveness is constrained by toxicity and adverse effects. The Lamiaceae herb Salvia miltiorrhiza Bunge has a long history of therapeutic use in the treatment of blood stasis illnesses, which are believed by traditional Chinese medicine to be connected to cancer. AIM OF THE STUDY This review summarized the common toxicity of chemotherapy and the potential chemo-adjuvant effect and mechanisms of active ingredients from S. miltiorrhiza, hoping to provide valuable information for the development and application of S. miltiorrhiza resources. MATERIALS AND METHODS The literatures were retrieved from PubMed, Web of Science, Baidu Scholar and Google Scholar databases from 2002 to 2022. The inclusion criteria were studies reporting that S. miltiorrhiza or its constituents enhanced the efficiency of chemotherapy drugs or reduced the side effects. RESULTS Salvianolic acid A, salvianolic acid B, salvianolic acid C, rosmarinic acid, tanshinone I, tanshinone IIA, cryptotanshinone, dihydrotanshinone I and miltirone are the primary adjuvant chemotherapy components of S. miltiorrhiza. The mechanisms mainly involve inhibiting proliferation, metastasis, and angiogenesis, inducing apoptosis, regulating autophagy and tumor microenvironment. In addition, they also improve chemotherapy drug-induced side effects. CONCLUSIONS The bioactive compounds of S. miltiorrhiza are shown to inhibit proliferation, metastasis, and angiogenesis, induce apoptosis and autophagy, regulate immunity and tumor microenvironment when combined with chemotherapy drugs. However, further clinical studies are required to validate the current studies.
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Affiliation(s)
- Jiayan Huang
- Laboratory for Core Technology of TCM Quality Improvement and Transformation, School of Pharmaceutical Science, The Third Affiliated Hospital, Academy of Chinese Medical Science, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
| | - Jiaojiao Zhang
- College of Food and Health, Zhejiang A&F University, Hangzhou, 311300, China.
| | - Chengtao Sun
- College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
| | - Ruiwen Yang
- Laboratory for Core Technology of TCM Quality Improvement and Transformation, School of Pharmaceutical Science, The Third Affiliated Hospital, Academy of Chinese Medical Science, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
| | - Miaomiao Sheng
- Laboratory for Core Technology of TCM Quality Improvement and Transformation, School of Pharmaceutical Science, The Third Affiliated Hospital, Academy of Chinese Medical Science, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
| | - Jiangning Hu
- Zhejiang Conba Pharmaceutical Limited Company, Zhejiang Provincial Key Laboratory of Traditional Chinese Medicine Pharmaceutical Technology, Hangzhou, 310052, China.
| | - Guoyin Kai
- Laboratory for Core Technology of TCM Quality Improvement and Transformation, School of Pharmaceutical Science, The Third Affiliated Hospital, Academy of Chinese Medical Science, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
| | - Bing Han
- Laboratory for Core Technology of TCM Quality Improvement and Transformation, School of Pharmaceutical Science, The Third Affiliated Hospital, Academy of Chinese Medical Science, Zhejiang Chinese Medical University, Hangzhou, 310053, China; Zhejiang Conba Pharmaceutical Limited Company, Zhejiang Provincial Key Laboratory of Traditional Chinese Medicine Pharmaceutical Technology, Hangzhou, 310052, China; College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
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Matsuoka T, Yashiro M. Molecular Insight into Gastric Cancer Invasion-Current Status and Future Directions. Cancers (Basel) 2023; 16:54. [PMID: 38201481 PMCID: PMC10778111 DOI: 10.3390/cancers16010054] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2023] [Revised: 12/15/2023] [Accepted: 12/20/2023] [Indexed: 01/12/2024] Open
Abstract
Gastric cancer (GC) is one of the most common malignancies worldwide. There has been no efficient therapy for stage IV GC patients due to this disease's heterogeneity and dissemination ability. Despite the rapid advancement of molecular targeted therapies, such as HER2 and immune checkpoint inhibitors, survival of GC patients is still unsatisfactory because the understanding of the mechanism of GC progression is still incomplete. Invasion is the most important feature of GC metastasis, which causes poor mortality in patients. Recently, genomic research has critically deepened our knowledge of which gene products are dysregulated in invasive GC. Furthermore, the study of the interaction of GC cells with the tumor microenvironment has emerged as a principal subject in driving invasion and metastasis. These results are expected to provide a profound knowledge of how biological molecules are implicated in GC development. This review summarizes the advances in our current understanding of the molecular mechanism of GC invasion. We also highlight the future directions of the invasion therapeutics of GC. Compared to conventional therapy using protease or molecular inhibitors alone, multi-therapy targeting invasion plasticity may seem to be an assuring direction for the progression of novel strategies.
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Affiliation(s)
| | - Masakazu Yashiro
- Molecular Oncology and Therapeutics, Osaka Metropolitan University Graduate School of Medicine, Osaka 5458585, Japan;
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Chen B, Dong X, Zhang J, Wang W, Song Y, Sun X, Zhao K, Sun Z. Effects of oxidative stress regulation in inflammation-associated gastric cancer progression treated using traditional Chinese medicines: A review. Medicine (Baltimore) 2023; 102:e36157. [PMID: 37986311 PMCID: PMC10659735 DOI: 10.1097/md.0000000000036157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Revised: 10/25/2023] [Accepted: 10/26/2023] [Indexed: 11/22/2023] Open
Abstract
Gastric cancer (GC) is a global public health concern that poses a serious threat to human health owing to its high morbidity and mortality rates. Due to the lack of specificity of symptoms, patients with GC tend to be diagnosed at an advanced stage with poor prognosis. Therefore, the development of new treatment methods is particularly urgent. Chronic atrophic gastritis (CAG), a precancerous GC lesion, plays a key role in its occurrence and development. Oxidative stress has been identified as an important factor driving the development and progression of the pathological processes of CAG and GC. Therefore, regulating oxidative stress pathways can not only intervene in CAG development but also prevent the occurrence and metastasis of GC and improve the prognosis of GC patients. In this study, PubMed, CNKI, and Web of Science were used to search for a large number of relevant studies. The review results suggested that the active ingredients of traditional Chinese medicine (TCM) and TCM prescriptions could target and improve inflammation, pathological status, metastasis, and invasion of tumor cells, providing a potential new supplement for the treatment of CAG and GC.
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Affiliation(s)
- Bo Chen
- Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China
| | - Xinqian Dong
- Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China
| | - Jinlong Zhang
- Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China
| | - Wei Wang
- Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China
| | - Yujiao Song
- Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China
| | - Xitong Sun
- Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China
| | - Kangning Zhao
- Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China
| | - Zhen Sun
- Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China
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He G, Chen G, Liu W, Ye D, Liu X, Liang X, Song J. Salvianolic Acid B: A Review of Pharmacological Effects, Safety, Combination Therapy, New Dosage Forms, and Novel Drug Delivery Routes. Pharmaceutics 2023; 15:2235. [PMID: 37765204 PMCID: PMC10538146 DOI: 10.3390/pharmaceutics15092235] [Citation(s) in RCA: 31] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Revised: 08/23/2023] [Accepted: 08/25/2023] [Indexed: 09/29/2023] Open
Abstract
Salvianolic acid B is extracted from the roots and rhizomes of Danshen (Salvia miltiorrhiza Bge., family Labiatae). It is a water-soluble, weakly acidic drug that has demonstrated antitumor and anti-inflammatory effects on various organs and tissues such as the lung, heart, kidney, intestine, bone, liver, and skin and protective effects in diseases such as depression and spinal cord injury. The mechanisms underlying the protective effects of salvianolic acid B are mainly related to its anti-inflammatory, antioxidant, anti- or pro-apoptotic, anti- or pro-autophagy, anti-fibrotic, and metabolism-regulating functions. Salvianolic acid B can regulate various signaling pathways, cells, and molecules to achieve maximum therapeutic effects. This review summarizes the safety profile, combination therapy potential, and new dosage forms and delivery routes of salvianolic acid B. Although significant research progress has been made, more in-depth pharmacological studies are warranted to identify the mechanism of action, related signaling pathways, more suitable combination drugs, more effective dosage forms, and novel routes of administration of salvianolic acid B.
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Affiliation(s)
- Guannan He
- Shandong University of Traditional Chinese Medicine, Jinan 250355, China; (G.H.); (W.L.); (D.Y.)
| | - Guangfeng Chen
- Department of Geriatrics, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250355, China;
| | - Weidong Liu
- Shandong University of Traditional Chinese Medicine, Jinan 250355, China; (G.H.); (W.L.); (D.Y.)
| | - Dongxue Ye
- Shandong University of Traditional Chinese Medicine, Jinan 250355, China; (G.H.); (W.L.); (D.Y.)
| | - Xuehuan Liu
- Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan 250355, China;
| | - Xiaodong Liang
- Shandong University of Traditional Chinese Medicine, Jinan 250355, China; (G.H.); (W.L.); (D.Y.)
| | - Jing Song
- Shandong University of Traditional Chinese Medicine, Jinan 250355, China; (G.H.); (W.L.); (D.Y.)
- Shandong Yuze Pharmaceutical Industry Technology Research Institute Co., Ltd., Dezhou 251200, China
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Zhu Y, Wang S, Niu P, Chen H, Zhou J, Jiang L, Li D, Shi D. Raptor couples mTORC1 and ERK1/2 inhibition by cardamonin with oxidative stress induction in ovarian cancer cells. PeerJ 2023; 11:e15498. [PMID: 37304865 PMCID: PMC10257395 DOI: 10.7717/peerj.15498] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2023] [Accepted: 05/12/2023] [Indexed: 06/13/2023] Open
Abstract
Background A balance on nutrient supply and redox homeostasis is required for cell survival, and increased antioxidant capacity of cancer cells may lead to chemotherapy failure. Objective To investigate the mechanism of anti-proliferation of cardamonin by inducing oxidative stress in ovarian cancer cells. Methods After 24 h of drug treatment, CCK8 kit and wound healing test were used to detect cell viability and migration ability, respectively, and the ROS levels were detected by flow cytometry. The differential protein expression after cardamonin administration was analyzed by proteomics, and the protein level was detected by Western blotting. Results Cardamonin inhibited the cell growth, which was related to ROS accumulation. Proteomic analysis suggested that MAPK pathway might be involved in cardamonin-induced oxidative stress. Western blotting showed that cardamonin decreased Raptor expression and the activity of mTORC1 and ERK1/2. Same results were observed in Raptor KO cells. Notably, in Raptor KO cells, the effect of cardamonin was weakened. Conclusion Raptor mediated the function of cardamonin on cellular redox homeostasis and cell proliferation through mTORC1 and ERK1/2 pathways.
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12
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Natural and synthetic compounds for glioma treatment based on ROS-mediated strategy. Eur J Pharmacol 2023:175537. [PMID: 36871663 DOI: 10.1016/j.ejphar.2023.175537] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2022] [Revised: 01/08/2023] [Accepted: 01/23/2023] [Indexed: 03/06/2023]
Abstract
Glioma is the most frequent and most malignant tumor of the central nervous system (CNS)，accounting for about 50% of all CNS tumor and approximately 80% of the malignant primary tumors in the CNS. Patients with glioma benefit from surgical resection, chemo- and radio-therapy. However these therapeutical strategies do not significantly improve the prognosis, nor increase survival rates owing to restricted drug contribution in the CNS and to the malignant characteristics of glioma. Reactive oxygen species (ROS) are important oxygen-containing molecules that regulate tumorigenesis and tumor progression. When ROS accumulates to cytotoxic levels, this can lead to anti-tumor effects. Multiple chemicals used as therapeutic strategies are based on this mechanism. They regulate intracellular ROS levels directly or indirectly, resulting in the inability of glioma cells to adapt to the damage induced by these substances. In the current review, we summarize the natural products, synthetic compounds and interdisciplinary techniques used for the treatment of glioma. Their possible molecular mechanisms are also presented. Some of them are also used as sensitizers: they modulate ROS levels to improve the outcomes of chemo- and radio-therapy. In addition, we summarize some new targets upstream or downstream of ROS to provide ideas for developing new anti-glioma therapies.
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Guo SS, Wang ZG. Salvianolic acid B from Salvia miltiorrhiza bunge: A potential antitumor agent. Front Pharmacol 2022; 13:1042745. [PMID: 36386172 PMCID: PMC9640750 DOI: 10.3389/fphar.2022.1042745] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Accepted: 10/14/2022] [Indexed: 11/25/2022] Open
Abstract
Salvia miltiorrhiza Bunge (Lamiaceae) is a perennial herb widely found in China since ancient times with a high economic and medicinal value. Salvianolic acid B (Sal-B) is an important natural product derived from Salvia miltiorrhiza and this review summarizes the anticancer activity of Sal-B. Sal-B inhibits tumor growth and metastasis by targeting multiple cell signaling pathways. This review aims to review experimental studies to describe the possible anticancer mechanisms of Sal-B and confirm its potential as a therapeutic drug.
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Affiliation(s)
- Sha-Sha Guo
- Key Laboratory of Theory of TCM, Ministry of Education of China, Shandong University of Traditional Chinese Medicine, Jinan, China
- Institute of Traditional Chinese Medicine Literature and Culture, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Zhen-Guo Wang
- Key Laboratory of Theory of TCM, Ministry of Education of China, Shandong University of Traditional Chinese Medicine, Jinan, China
- Institute of Traditional Chinese Medicine Literature and Culture, Shandong University of Traditional Chinese Medicine, Jinan, China
- *Correspondence: Zhen-Guo Wang,
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Lu M, Lan X, Wu X, Fang X, Zhang Y, Luo H, Gao W, Wu D. Salvia miltiorrhiza in cancer: Potential role in regulating MicroRNAs and epigenetic enzymes. Front Pharmacol 2022; 13:1008222. [PMID: 36172186 PMCID: PMC9512245 DOI: 10.3389/fphar.2022.1008222] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2022] [Accepted: 08/24/2022] [Indexed: 11/21/2022] Open
Abstract
MicroRNAs are small non-coding RNAs that play important roles in gene regulation by influencing the translation and longevity of various target mRNAs and the expression of various target genes as well as by modifying histones and DNA methylation of promoter sites. Consequently, when dysregulated, microRNAs are involved in the development and progression of a variety of diseases, including cancer, by affecting cell growth, proliferation, differentiation, migration, and apoptosis. Preparations from the dried root and rhizome of Salvia miltiorrhiza Bge (Lamiaceae), also known as red sage or danshen, are widely used for treating cardiovascular diseases. Accumulating data suggest that certain bioactive constituents of this plant, particularly tanshinones, have broad antitumor effects by interfering with microRNAs and epigenetic enzymes. This paper reviews the evidence for the antineoplastic activities of S. miltiorrhiza constituents by causing or promoting cell cycle arrest, apoptosis, autophagy, epithelial-mesenchymal transition, angiogenesis, and epigenetic changes to provide an outlook on their future roles in the treatment of cancer, both alone and in combination with other modalities.
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Affiliation(s)
- Meng Lu
- School of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
| | - Xintian Lan
- School of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
| | - Xi Wu
- School of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
| | - Xiaoxue Fang
- School of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
| | - Yegang Zhang
- School of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
| | - Haoming Luo
- School of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
- Key Laboratory of Effective Components of Traditional Chinese Medicine, Changchun, China
| | - Wenyi Gao
- School of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
- *Correspondence: Wenyi Gao, ; Donglu Wu,
| | - Donglu Wu
- Key Laboratory of Effective Components of Traditional Chinese Medicine, Changchun, China
- School of Clinical Medical, Changchun University of Chinese Medicine, Changchun, China
- *Correspondence: Wenyi Gao, ; Donglu Wu,
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Salvianolic Acid B Suppresses Non-Small-Cell Lung Cancer Metastasis through PKM2-Independent Metabolic Reprogramming. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:9302403. [PMID: 35502178 PMCID: PMC9056207 DOI: 10.1155/2022/9302403] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Accepted: 03/25/2022] [Indexed: 12/26/2022]
Abstract
Objective Salvianolic acid B (Sal B) has been demonstrated to be a potential chemoprevention agent for several cancers. Herein, we investigated the pharmacological function of Sal B on non-small-cell lung cancer (NSCLC) metastasis. Methods Two NSCLC cell lines (NCI-H2030 and NCI-H1650) were disposed of by 200 μM Sal B or 10 μM PKM2 agonist TEPP-46. Wound healing and transwell experiments were implemented for analyzing migratory and invasive capacities. Epithelial-to-mesenchymal transition (EMT) markers β-catenin and E-cadherin were measured via western blotting. Cellular bioenergetics were evaluated with glucose uptake, lactate production, enolase activity, cellular ATP levels, as well as seahorse-based oxygen consumption rate (OCR), extracellular acidification rate (ECAR) analysis. Metabolic reprogramming markers PKM2, LDHA, and GLUT1 were detected via western blotting and immunofluorescence. Results The results showed that Sal B disposal weakened the migration and invasion of NCI-H2030 and NCI-H1650 cells and inactivated the EMT process according to downregulation of β-catenin and upregulation of E-cadherin. Sal B-treated NSCLC cells displayed decreased glucose uptake, lactate production, enolase activity, cellular ATP levels, OCR, and ECAR, indicating a reduction in metabolic reprogramming. Additionally, Sal B downregulated the expression of PKM2, LDHA, and GLUT1. TEPP-46 may reverse the inhibitory effect of Sal B on metastasis as well as metabolic reprogramming. Conclusion Our findings provide evidence that Sal B enables to weaken NSCLC metastasis through PKM2-independent metabolic reprogramming, which sheds light on the promising therapeutic usage of Sal B in treating NSCLC.
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Ai K, Yuan D, Zheng J. Experimental Research on the Antitumor Effect of Human Gastric Cancer Cells Transplanted in Nude Mice Based on Deep Learning Combined with Spleen-Invigorating Chinese Medicine. COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2022; 2022:3010901. [PMID: 35190750 PMCID: PMC8858057 DOI: 10.1155/2022/3010901] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Revised: 01/03/2022] [Accepted: 01/28/2022] [Indexed: 12/26/2022]
Abstract
Gastric cancer is still the fifth most common malignant tumor in the world and has the fourth highest mortality rate in the world. Gastric cancer is difficult to treat because of its unobvious onset, low resection rate, and rapid deterioration. Therefore, humans have been working hard to combat gastric cancer. At present, the most commonly used treatment method is radiotherapy. However, this method will damage the normal tissues of the irradiated area while treating malignant tumor cells. It not only has side effects of damage to the patient's skin and mucous membranes but also needs high-rate radiotherapy and has high cost for chemotherapy. In order to solve these problems, it is necessary to find new treatment methods. This article proposes the use of Chinese medicine to invigorate the spleen to inhibit human gastric cancer cells. This article combines modern machine learning technology with traditional Chinese medicine and combines traditional Chinese medicine physiotherapy with Western medicine nude mouse transplantation experiments. The treatment of tumors in Chinese medicine is based on the theory of Chinese medicine and has different characteristics. Western medicine has the advantage of permanently injuring patients. The process of the experiment is to transplant human-derived gastric cancer cells into nude mice. After grouping treatments and obtaining comparative data, deep learning techniques are used to analyze the properties of Chinese medicines for strengthening the spleen and to compare the properties of Chinese medicines for strengthening the spleen. The experimental results showed that the tumor inhibition rate of mice using fluorouracil was 18%, the tumor inhibition rate of mice using low-dose Chinese medicine was 16%, and the tumor inhibition rate of mice using high-dose Chinese medicine reached 52%. 80 days after the experiment, the survival rate of mice using high-dose Chinese medicine is 100% higher than that of mice without treatment.
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Affiliation(s)
- Ke Ai
- Medical College, China Three Gorges University, Yichang, 443000 Hubei, China
| | - Ding Yuan
- Medical College, China Three Gorges University, Yichang, 443000 Hubei, China
- Third-Grade Pharmacological Laboratory on TCM Approved by the State Administration of Traditional Chinese Medicine, China Three Gorges University, Yichang, 443000 Hubei, China
| | - Jie Zheng
- Medical College, China Three Gorges University, Yichang, 443000 Hubei, China
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Gierlikowska B, Stachura A, Gierlikowski W, Demkow U. Phagocytosis, Degranulation and Extracellular Traps Release by Neutrophils-The Current Knowledge, Pharmacological Modulation and Future Prospects. Front Pharmacol 2021; 12:666732. [PMID: 34017259 PMCID: PMC8129565 DOI: 10.3389/fphar.2021.666732] [Citation(s) in RCA: 67] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Accepted: 04/19/2021] [Indexed: 12/15/2022] Open
Abstract
Neutrophils are crucial elements of innate immune system, which assure host defense via a range of effector functions, such as phagocytosis, degranulation, and NET formation. The latest literature clearly indicates that modulation of effector functions of neutrophils may affect the treatment efficacy. Pharmacological modulation may affect molecular mechanisms activating or suppressing phagocytosis, degranulation or NET formation. In this review, we describe the role of neutrophils in physiology and in the course of bacterial and viral infections, illustrating the versatility and plasticity of those cells. This review also focus on the action of plant extracts, plant-derived compounds and synthetic drugs on effector functions of neutrophils. These recent advances in the knowledge can help to devise novel therapeutic approaches via pharmacological modulation of the described processes.
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Affiliation(s)
- Barbara Gierlikowska
- Department of Laboratory Diagnostics and Clinical Immunology of Developmental Age, Medical University of Warsaw, Warsaw, Poland
| | - Albert Stachura
- Department of Methodology, Centre for Preclinical Research, Medical University of Warsaw, Warsaw, Poland.,Doctoral School, Medical University of Warsaw, Warsaw, Poland
| | - Wojciech Gierlikowski
- Department of Internal Medicine and Endocrinology, Medical University of Warsaw, Warsaw, Poland
| | - Urszula Demkow
- Department of Laboratory Diagnostics and Clinical Immunology of Developmental Age, Medical University of Warsaw, Warsaw, Poland
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