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Utpal BK, Dehbia Z, Zidan BMRM, Sweilam SH, Singh LP, Arunkumar MS, Sona M, Panigrahy UP, Keerthana R, Mandadi SR, Rab SO, Alshehri MA, Koula D, Suliman M, Nafady MH, Emran TB. Carotenoids as modulators of the PI3K/Akt/mTOR pathway: innovative strategies in cancer therapy. Med Oncol 2024; 42:4. [PMID: 39549201 DOI: 10.1007/s12032-024-02551-x] [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: 09/20/2024] [Accepted: 10/29/2024] [Indexed: 11/18/2024]
Abstract
Cancer progression is primarily driven by the uncontrolled activation of cellular signaling pathways, with the PI3K/Akt/mTOR (PAMT) pathway playing a central role. This pathway significantly contributes to the proliferation and survival of cancer cells, and its hyperactivity is a major challenge in managing several types of malignancies. This article delves into the promising potential of carotenoids, natural pigments found in abundance in fruits and vegetables, as a novel therapeutic strategy for cancer treatment. By specifically targeting and inhibiting the PAMT pathway, carotenoids may effectively disrupt the growth and survival of cancer cells. The article examines the complex mechanisms underlying these interactions and highlights the obstacles faced in cancer treatment. It proposes a compelling approach to developing therapies that leverage natural products to target this critical pathway, offering a fresh perspective on cancer treatment. Further research is essential to enhance the therapeutic efficacy of these compounds.
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Affiliation(s)
- Biswajit Kumar Utpal
- Department of Pharmacy, Faculty of Health and Life Sciences, Daffodil International University, Dhaka, 1207, Bangladesh
| | - Zerrouki Dehbia
- Laboratory of AgroBiotechnology and Nutrition in Semi Arid Zones, Faculty of Nature and Life Sciences, University of Ibn Khaldoun, Tiaret, Algeria
| | - B M Redwan Matin Zidan
- Department of Pharmacy, Faculty of Pharmacy, University of Dhaka, Dhaka, 1000, Bangladesh
| | - Sherouk Hussein Sweilam
- Department of Pharmacognosy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, 11942, Saudi Arabia
- Department of Pharmacognosy, Faculty of Pharmacy, Egyptian Russian University, Cairo-Suez Road, Badr City, Cairo, 11829, Egypt
| | - Laliteshwar Pratap Singh
- Department of Pharmaceutical Chemistry, Narayan Institute of Pharmacy, Gopal Narayan Singh University, Sasaram (Rohtas) Bihar, Jamuhar, 821305, India
| | - M S Arunkumar
- Faculty of Pharmacy, Karpagam Academy of Higher Education, Coimbatore, Tamil Nadu, 641021, India
| | - M Sona
- Faculty of Pharmacy, Karpagam Academy of Higher Education, Coimbatore, Tamil Nadu, 641021, India
| | - Uttam Prasad Panigrahy
- Faculty of Pharmaceutical Science, Assam Down Town University, Gandhi Nagar, Sankar Madhab Path, Panikhaiti, Guwahati, Assam, India
| | - R Keerthana
- Faculty of Pharmacy, Karpagam Academy of Higher Education, Coimbatore, Tamil Nadu, 641021, India
| | - Sandhya Rani Mandadi
- Department of Pharmaceutics, Vishnu Institute of Pharmaceutical Education and Research, Tuljaraopet, Telangana , 502313, India
| | - Safia Obaidur Rab
- Department of Clinical Laboratory Sciences, College of Applied Medical Science, King Khalid University, Abha, Saudi Arabia
| | - Mohammed Ali Alshehri
- Department of Biology, Faculty of Science, University of Tabuk, Tabuk, 71491, Saudi Arabia
| | - Doukani Koula
- Laboratory of AgroBiotechnology and Nutrition in Semi Arid Zones, Faculty of Nature and Life Sciences, University of Ibn Khaldoun, Tiaret, Algeria
- Laboratory of Animal Production Sciences and Techniques, University of Abdelhamid Ibn Badis, Mostaganem, Algeria
| | - Muath Suliman
- Department of Clinical Laboratory Sciences, College of Applied Medical Science, King Khalid University, Abha, Saudi Arabia
| | - Mohamed H Nafady
- Faculty of Applied Health Science Technology, Misr University for Science and Technology, Giza, 12568, Egypt.
| | - Talha Bin Emran
- Department of Pharmacy, Faculty of Health and Life Sciences, Daffodil International University, Dhaka, 1207, Bangladesh
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Wang C, Huang X, Sun K, Li X, Feng D, Nakamura Y, Qi H. Whey protein and flaxseed gum co-encapsulated fucoxanthin promoted tumor cells apoptosis based on MAPK-PI3K/Akt regulation on Huh-7 cell xenografted nude mice. Int J Biol Macromol 2024; 278:134838. [PMID: 39159798 DOI: 10.1016/j.ijbiomac.2024.134838] [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: 06/28/2024] [Revised: 08/15/2024] [Accepted: 08/15/2024] [Indexed: 08/21/2024]
Abstract
Fucoxanthin (FX), a non-provitamin-A carotenoid, is a well-known major xanthophyll contained in edible brown algae. The nanoencapsulation of FX was motivated due to its multiple activities. Here, nano-encapsulated-FX (nano-FX) was prepared according to our early method by using whey protein and flaxseed gum as the biomacromolecule carrier material, then in vivo antitumor effect and mechanism of nano-FX on xenograft mice were investigated. Thirty 4-week-old male BALB/c nude mice were fed adaptively for 7 days to establish xenograft tumor model with Huh-7 cells. The tumor-bearing mice consumed nano-FX (50, 25, and 12.5 mg kg-1) and doxorubicin hydrochloride (DOX, 1 mg kg-1) or did not consume (Control) for 21 days, n = 6. The tumor inhibition rates of nano-FX were as high as 54.67 ± 1.04 %. Nano-FX intervention promoted apoptosis and induced hyperchromatic pyknosis and focal necrosis in tumor tissue by down-regulating the expression of p-JNK, p-ERK, PI3Kp85α, p-AKT, p-p38MAPK, Bcl-2, CyclinD1 and Ki-67, while up-regulating the expression of cleaved caspase-3 and Bax. Nano-FX inhibited tumor growth and protected liver function of tumor bearing mice in a dose-dependent manner, up-regulate the level of apoptosis-related proteins, inhibit the MAPK-PI3K/Akt pathways, and promote tumor cell apoptosis.
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Affiliation(s)
- Chunyan Wang
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, China; School of Food Science, Henan Institute of Science and Technology, Xinxiang 453003, China; SKL of Marine Food Processing & Safety Control, National Engineering Research Center of Seafood, Collaborative Innovation Center of Seafood Deep Processing, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, China
| | - Xu Huang
- SKL of Marine Food Processing & Safety Control, National Engineering Research Center of Seafood, Collaborative Innovation Center of Seafood Deep Processing, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, China
| | - Kailing Sun
- SKL of Marine Food Processing & Safety Control, National Engineering Research Center of Seafood, Collaborative Innovation Center of Seafood Deep Processing, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, China
| | - Xiang Li
- SKL of Marine Food Processing & Safety Control, National Engineering Research Center of Seafood, Collaborative Innovation Center of Seafood Deep Processing, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, China
| | - Dingding Feng
- SKL of Marine Food Processing & Safety Control, National Engineering Research Center of Seafood, Collaborative Innovation Center of Seafood Deep Processing, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, China
| | - Yoshimasa Nakamura
- Graduate School of Environmental and Life Science, Okayama University, Okayama, Japan
| | - Hang Qi
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, China; SKL of Marine Food Processing & Safety Control, National Engineering Research Center of Seafood, Collaborative Innovation Center of Seafood Deep Processing, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, China.
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Vijayarathna S, Oon CE, Al-Zahrani M, Abualreesh MH, Chen Y, Kanwar JR, Sahreen S, Ghazanfar S, Adnan M, Sasidharan S. Standardized Polyalthia longifolia leaf extract induces the apoptotic HeLa cells death via microRNA regulation: identification, validation, and therapeutic potential. Front Pharmacol 2023; 14:1198425. [PMID: 37693900 PMCID: PMC10483226 DOI: 10.3389/fphar.2023.1198425] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2023] [Accepted: 08/02/2023] [Indexed: 09/12/2023] Open
Abstract
Polyalthia longifolia var. angustifolia Thw. (Annonaceae), is a famous traditional medicinal plant in Asia. Ample data specifies that the medicinal plant P. longifolia has anticancer activity; however, the detailed mechanisms of action still need to be well studied. Recent studies have revealed the cytotoxicity potential of P. longifolia leaf against HeLa cells. Therefore, the current study was conducted to examine the regulation of miRNAs in HeLa cancer cells treated with the standardized P. longifolia methanolic leaf extract (PLME). The regulation of miRNAs in HeLa cancer cells treated with the standardized PLME extract was studied through Illumina, Hi-Seq. 2000 platform of Next-Generation Sequencing (NGS) and various in silico bioinformatics tools. The PLME treatment regulated a subset of miRNAs in HeLa cells. Interestingly, the PLME treatment against HeLa cancer cells identified 10 upregulated and 43 downregulated (p < 0.05) miRNAs associated with apoptosis induction. Gene ontology (GO) term analysis indicated that PLME induces cell death in HeLa cells by inducing the pro-apoptotic genes. Moreover, the downregulated oncomiRs modulated by PLME treatment in HeLa cells were identified, targeting apoptosis-related genes through gene ontology and pathway analysis. The LC-ESI-MS/MS analysis identified the presence of Vidarabine and Anandamide compounds that were previously reported to exhibit anticancer activity. The findings of this study obviously linked the cell cytotoxicity effect of PLME treatment against the HeLa cells with regulating various miRNAs expression related to apoptosis induction in the HeLa cells. PLME treatment induced apoptotic HeLa cell death mechanism by regulating multiple miRNAs. The identified miRNAs regulated by PLME may provide further insight into the mechanisms that play a critical role in cervical cancer, as well as novel ideas regarding gene therapeutic strategies.
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Affiliation(s)
- Soundararajan Vijayarathna
- Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, Pulau Pinang, Malaysia
| | - Chern Ein Oon
- Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, Pulau Pinang, Malaysia
| | - Majid Al-Zahrani
- Biological Sciences Department, College of Science and Arts, King Abdulaziz University, Rabigh, Saudi Arabia
| | - Muyassar H. Abualreesh
- Department of Marine Biology, Faculty of Marine Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Yeng Chen
- Department of Oral and Craniofacial Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia
| | - Jagat R. Kanwar
- Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Bilaspur, India
| | - Sumaira Sahreen
- Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, Pulau Pinang, Malaysia
| | - Shakira Ghazanfar
- National Institute of Genomics and Advanced Biotechnology (NIGAB), National Agriculture Research Centre (NARC), Islamabad, Pakistan
| | - Mohd Adnan
- Department of Biology, College of Science, University of Ha’il, Ha’il, Saudi Arabia
| | - Sreenivasan Sasidharan
- Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, Pulau Pinang, Malaysia
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Chini Zittelli G, Lauceri R, Faraloni C, Silva Benavides AM, Torzillo G. Valuable pigments from microalgae: phycobiliproteins, primary carotenoids, and fucoxanthin. Photochem Photobiol Sci 2023; 22:1733-1789. [PMID: 37036620 DOI: 10.1007/s43630-023-00407-3] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Accepted: 03/03/2023] [Indexed: 04/11/2023]
Abstract
Phycobiliproteins, carotenoids and fucoxanthin are photosynthetic pigments extracted from microalgae and cyanobacteria with great potential biotechnological applications, as healthy food colorants and cosmetics. Phycocyanin possesses a brilliant blue color, with fluorescent properties making it useful as a reagent for immunological essays. The most important source of phycocyanin is the cyanobacterium Arthrospira platensis, however, recently, the Rhodophyta Galdieria sulphuraria has also been identified as such. The main obstacle to the commercialization of phycocyanin is represented by its chemical instability, strongly reducing its shelf-life. Moreover, the high level of purity needed for pharmaceutical applications requires several steps which increase both the production time and cost. Microalgae (Chlorella, Dunaliella, Nannochloropsis, Scenedesmus) produce several light harvesting carotenoids, and are able to manage with oxidative stress, due to their free radical scavenging properties, which makes them suitable for use as source of natural antioxidants. Many studies focused on the selection of the most promising strains producing valuable carotenoids and on their extraction and purification. Among carotenoids produced by marine microalgae, fucoxanthin is the most abundant, representing more than 10% of total carotenoids. Despite the abundance and diversity of fucoxanthin producing microalgae only a few species have been studied for commercial production, the most relevant being Phaeodactylum tricornutum. Due to its antioxidant activity, fucoxanthin can bring various potential benefits to the prevention and treatment of lifestyle-related diseases. In this review, we update the main results achieved in the production, extraction, purification, and commercialization of these important pigments, motivating the cultivation of microalgae as a source of natural pigments.
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Affiliation(s)
- Graziella Chini Zittelli
- Istituto per la Bioeconomia, CNR, Via Madonna del Piano 10, 50019, Sesto Fiorentino, Florence, Italy
| | - Rosaria Lauceri
- Istituto di Ricerca sulle Acque, CNR, Sede Di Verbania, Largo Tonolli 50, 28922, Verbania, Italy
| | - Cecilia Faraloni
- Istituto per la Bioeconomia, CNR, Via Madonna del Piano 10, 50019, Sesto Fiorentino, Florence, Italy
| | - Ana Margarita Silva Benavides
- Centro de Investigación en Ciencias del Mar Y Limnologίa, Universidad de Costa Rica, San Pedro, San José, 2060, Costa Rica
- Escuela de Biologia, Universidad de Costa Rica, San Pedro, San José, 2060, Costa Rica
| | - Giuseppe Torzillo
- Istituto per la Bioeconomia, CNR, Via Madonna del Piano 10, 50019, Sesto Fiorentino, Florence, Italy.
- Centro de Investigación en Ciencias del Mar Y Limnologίa, Universidad de Costa Rica, San Pedro, San José, 2060, Costa Rica.
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Liu F, Xu J, Yang R, Liu S, Hu S, Yan M, Han F. New light on treatment of cervical cancer: Chinese medicine monomers can be effective for cervical cancer by inhibiting the PI3K/Akt signaling pathway. Biomed Pharmacother 2023; 157:114084. [PMID: 36481407 DOI: 10.1016/j.biopha.2022.114084] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Revised: 11/27/2022] [Accepted: 12/02/2022] [Indexed: 12/12/2022] Open
Abstract
Cervical cancer (CC), as the most common malignant tumor of the female reproductive system, is infamous for its high morbidity and mortality rates. Its development and metastasis are intricate because numerous signaling pathways are involved. Since the cancer and the PI3K/Akt signaling pathway are closely intertwined, direct inhibition of either the PI3K/Akt pathway or its target genes and molecules may be remarkably constructive for treatment. Albeit remarkable advances in the treatment of CC, existing common anti-cancer medications are not without problems. These problems include myelotoxicity, cardiotoxicity, genotoxicity, and vasospasm, which are the most common and well-recognized toxicities associated with these medications. Therefore, it is necessary and urgent to develop novel, potent, secure, and more reasonably priced anticancer medications that are void of the above problems. Against this backdrop, Chinese medicine monomers have received more attention in recent years owing to their safety, low toxicity, few side effects, and anti-tumor properties. By regulating the PI3K/Akt signaling pathway, Chinese medicine monomers are effective not only in inhibiting CC growth, proliferation, apoptosis, invasion, migration, and reversing drug resistance but also in a variety of targets. Most previous earlier studies focused on the use of a single traditional Chinese medicine monomer to treat CC by regulating the PI3K/Akt signaling pathway rather than a combination of several such monomers. More importantly, to our knowledge, there has hardly been any study providing an exhaustive and comprehensive review of all the Chinese medicine monomers at CC. In response to this scarcity, we attempt in this paper to provide a comprehensive review of all the literature to date on traditional Chinese medicine monomers at cervical cancer, highlight the mechanisms and future prospects for their use in the prevention and treatment of cervical cancer.
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Affiliation(s)
- Fangyuan Liu
- Heilongjiang University of Chinese Medicine, Harbin 150040, China
| | - Jiayue Xu
- Xi'an Hospital of Chinese Medicine, Xi'an 710021, China
| | - Rui Yang
- Heilongjiang University of Chinese Medicine, Harbin 150040, China
| | - Shaoxuan Liu
- Heilongjiang University of Chinese Medicine, Harbin 150040, China
| | - Siya Hu
- Heilongjiang University of Chinese Medicine, Harbin 150040, China
| | - Mengyu Yan
- Heilongjiang University of Chinese Medicine, Harbin 150040, China
| | - Fengjuan Han
- The First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin 150040, China.
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Ahmed SA, Mendonca P, Elhag R, Soliman KFA. Anticancer Effects of Fucoxanthin through Cell Cycle Arrest, Apoptosis Induction, Angiogenesis Inhibition, and Autophagy Modulation. Int J Mol Sci 2022; 23:16091. [PMID: 36555740 PMCID: PMC9785196 DOI: 10.3390/ijms232416091] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Revised: 12/09/2022] [Accepted: 12/12/2022] [Indexed: 12/23/2022] Open
Abstract
Cancer accounts for one in seven deaths worldwide and is the second leading cause of death in the United States, after heart disease. One of the standard cancer treatments is chemotherapy which sometimes can lead to chemoresistance and treatment failure. Therefore, there is a great need for novel therapeutic approaches to treat these patients. Novel natural products have exhibited anticancer effects that may be beneficial in treating many kinds of cancer, having fewer side effects, low toxicity, and affordability. Numerous marine natural compounds have been found to inhibit molecular events and signaling pathways associated with various stages of cancer development. Fucoxanthin is a well-known marine carotenoid of the xanthophyll family with bioactive compounds. It is profusely found in brown seaweeds, providing more than 10% of the total creation of natural carotenoids. Fucoxanthin is found in edible brown seaweed macroalgae such as Undaria pinnatifida, Laminaria japonica, and Eisenia bicyclis. Many of fucoxanthin's pharmacological properties include antioxidant, anti-tumor, anti-inflammatory, antiobesity, anticancer, and antihypertensive effects. Fucoxanthin inhibits many cancer cell lines' proliferation, angiogenesis, migration, invasion, and metastasis. In addition, it modulates miRNA and induces cell cycle growth arrest, apoptosis, and autophagy. Moreover, the literature shows fucoxanthin's ability to inhibit cytokines and growth factors such as TNF-α and VEGF, which stimulates the activation of downstream signaling pathways such as PI3K/Akt autophagy, and pathways of apoptosis. This review highlights the different critical mechanisms by which fucoxanthin inhibits diverse cancer types, such as breast, prostate, gastric, lung, and bladder development and progression. Moreover, this article reviews the existing literature and provides critical supportive evidence for fucoxanthin's possible therapeutic use in cancer.
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Affiliation(s)
- Shade’ A. Ahmed
- Division of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Institute of Public Health, Florida A&M University, Tallahassee, FL 32307, USA
| | - Patricia Mendonca
- Department of Biology, College of Science and Technology, Florida A&M University, Tallahassee, FL 32307, USA
| | - Rashid Elhag
- Department of Biology, College of Science and Technology, Florida A&M University, Tallahassee, FL 32307, USA
| | - Karam F. A. Soliman
- Division of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Institute of Public Health, Florida A&M University, Tallahassee, FL 32307, USA
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Guan B, Chen K, Tong Z, Chen L, Chen Q, Su J. Advances in Fucoxanthin Research for the Prevention and Treatment of Inflammation-Related Diseases. Nutrients 2022; 14:nu14224768. [PMID: 36432455 PMCID: PMC9694790 DOI: 10.3390/nu14224768] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Revised: 11/01/2022] [Accepted: 11/10/2022] [Indexed: 11/16/2022] Open
Abstract
Owing to its unique structure and properties, fucoxanthin (FX), a carotenoid, has attracted significant attention. There have been numerous studies that demonstrate FX's anti-inflammatory, antioxidant, antitumor, and anti-obesity properties against inflammation-related diseases. There is no consensus, however, regarding the molecular mechanisms underlying this phenomenon. In this review, we summarize the potential health benefits of FX in inflammatory-related diseases, from the perspective of animal and cellular experiments, to provide insights for future research on FX. Previous work in our lab has demonstrated that FX remarkably decreased LPS-induced inflammation and improved survival in septic mice. Further investigation of the activity of FX against a wide range of diseases will require new approaches to uncover its molecular mechanism. This review will provide an outline of the current state of knowledge regarding FX application in the clinical setting and suggest future directions to implement FX as a therapeutic ingredient in pharmaceutical sciences in order to develop it into a treatment strategy against inflammation-associated disorders.
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Affiliation(s)
- Biyun Guan
- Fujian Key Laboratory of Innate Immune Biology, Biomedical Research Center of South China, College of Life Sciences, Fujian Normal University, Fuzhou 350117, China
| | - Kunsen Chen
- Fujian Key Laboratory of Innate Immune Biology, Biomedical Research Center of South China, College of Life Sciences, Fujian Normal University, Fuzhou 350117, China
| | - Zhiyong Tong
- Fujian Key Laboratory of Innate Immune Biology, Biomedical Research Center of South China, College of Life Sciences, Fujian Normal University, Fuzhou 350117, China
| | - Long Chen
- Department of Neurosurgery & Neurocritical Care, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Qi Chen
- Fujian Key Laboratory of Innate Immune Biology, Biomedical Research Center of South China, College of Life Sciences, Fujian Normal University, Fuzhou 350117, China
- Correspondence: (Q.C.); (J.S.); Tel./Fax: +86-0591-22868190 (Q.C.); +86-0591-22868830 (J.S.)
| | - Jingqian Su
- Fujian Key Laboratory of Innate Immune Biology, Biomedical Research Center of South China, College of Life Sciences, Fujian Normal University, Fuzhou 350117, China
- Correspondence: (Q.C.); (J.S.); Tel./Fax: +86-0591-22868190 (Q.C.); +86-0591-22868830 (J.S.)
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Din NAS, Mohd Alayudin ‘AS, Sofian-Seng NS, Rahman HA, Mohd Razali NS, Lim SJ, Wan Mustapha WA. Brown Algae as Functional Food Source of Fucoxanthin: A Review. Foods 2022; 11:2235. [PMID: 35954003 PMCID: PMC9368577 DOI: 10.3390/foods11152235] [Citation(s) in RCA: 44] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Revised: 07/17/2022] [Accepted: 07/20/2022] [Indexed: 02/06/2023] Open
Abstract
Fucoxanthin is an algae-specific xanthophyll of aquatic carotenoid. It is prevalent in brown seaweed because it functions as a light-harvesting complex for algal photosynthesis and photoprotection. Its exceptional chemical structure exhibits numerous biological activities that benefit human health. Due to these valuable properties, fucoxanthin's potential as a potent source for functional food, feed, and medicine is being explored extensively today. This article has thoroughly reviewed the availability and biosynthesis of fucoxanthin in the brown seaweed, as well as the mechanism behind it. We included the literature findings concerning the beneficial bioactivities of fucoxanthin such as antioxidant, anti-inflammatory, anti-obesity, antidiabetic, anticancer, and other potential activities. Last, an additional view on its potential as a functional food ingredient has been discussed to facilitate a broader application of fucoxanthin as a promising bioactive compound.
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Affiliation(s)
- Nur Akmal Solehah Din
- Department of Food Sciences, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Bangi 43600, Selangor, Malaysia; (N.A.S.D.); (‘A.S.M.A.); (N.-S.S.-S.); (H.A.R.); (N.S.M.R.); (S.J.L.)
| | - ‘Ain Sajda Mohd Alayudin
- Department of Food Sciences, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Bangi 43600, Selangor, Malaysia; (N.A.S.D.); (‘A.S.M.A.); (N.-S.S.-S.); (H.A.R.); (N.S.M.R.); (S.J.L.)
| | - Noor-Soffalina Sofian-Seng
- Department of Food Sciences, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Bangi 43600, Selangor, Malaysia; (N.A.S.D.); (‘A.S.M.A.); (N.-S.S.-S.); (H.A.R.); (N.S.M.R.); (S.J.L.)
- Innovation Centre for Confectionery Technology (MANIS), Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Bangi 43600, Selangor, Malaysia
| | - Hafeedza Abdul Rahman
- Department of Food Sciences, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Bangi 43600, Selangor, Malaysia; (N.A.S.D.); (‘A.S.M.A.); (N.-S.S.-S.); (H.A.R.); (N.S.M.R.); (S.J.L.)
- Innovation Centre for Confectionery Technology (MANIS), Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Bangi 43600, Selangor, Malaysia
| | - Noorul Syuhada Mohd Razali
- Department of Food Sciences, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Bangi 43600, Selangor, Malaysia; (N.A.S.D.); (‘A.S.M.A.); (N.-S.S.-S.); (H.A.R.); (N.S.M.R.); (S.J.L.)
- Innovation Centre for Confectionery Technology (MANIS), Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Bangi 43600, Selangor, Malaysia
| | - Seng Joe Lim
- Department of Food Sciences, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Bangi 43600, Selangor, Malaysia; (N.A.S.D.); (‘A.S.M.A.); (N.-S.S.-S.); (H.A.R.); (N.S.M.R.); (S.J.L.)
- Innovation Centre for Confectionery Technology (MANIS), Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Bangi 43600, Selangor, Malaysia
| | - Wan Aida Wan Mustapha
- Department of Food Sciences, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Bangi 43600, Selangor, Malaysia; (N.A.S.D.); (‘A.S.M.A.); (N.-S.S.-S.); (H.A.R.); (N.S.M.R.); (S.J.L.)
- Innovation Centre for Confectionery Technology (MANIS), Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Bangi 43600, Selangor, Malaysia
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Ávila-Román J, García-Gil S, Rodríguez-Luna A, Motilva V, Talero E. Anti-Inflammatory and Anticancer Effects of Microalgal Carotenoids. Mar Drugs 2021; 19:531. [PMID: 34677429 PMCID: PMC8539290 DOI: 10.3390/md19100531] [Citation(s) in RCA: 52] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Revised: 09/19/2021] [Accepted: 09/20/2021] [Indexed: 12/12/2022] Open
Abstract
Acute inflammation is a key component of the immune system's response to pathogens, toxic agents, or tissue injury, involving the stimulation of defense mechanisms aimed to removing pathogenic factors and restoring tissue homeostasis. However, uncontrolled acute inflammatory response may lead to chronic inflammation, which is involved in the development of many diseases, including cancer. Nowadays, the need to find new potential therapeutic compounds has raised the worldwide scientific interest to study the marine environment. Specifically, microalgae are considered rich sources of bioactive molecules, such as carotenoids, which are natural isoprenoid pigments with important beneficial effects for health due to their biological activities. Carotenoids are essential nutrients for mammals, but they are unable to synthesize them; instead, a dietary intake of these compounds is required. Carotenoids are classified as carotenes (hydrocarbon carotenoids), such as α- and β-carotene, and xanthophylls (oxygenate derivatives) including zeaxanthin, astaxanthin, fucoxanthin, lutein, α- and β-cryptoxanthin, and canthaxanthin. This review summarizes the present up-to-date knowledge of the anti-inflammatory and anticancer activities of microalgal carotenoids both in vitro and in vivo, as well as the latest status of human studies for their potential use in prevention and treatment of inflammatory diseases and cancer.
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Affiliation(s)
- Javier Ávila-Román
- Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, 43007 Tarragona, Spain
| | - Sara García-Gil
- Department of Pharmacology, Universidad de Sevilla, 41012 Seville, Spain; (S.G.-G.); (A.R.-L.); (V.M.)
| | - Azahara Rodríguez-Luna
- Department of Pharmacology, Universidad de Sevilla, 41012 Seville, Spain; (S.G.-G.); (A.R.-L.); (V.M.)
| | - Virginia Motilva
- Department of Pharmacology, Universidad de Sevilla, 41012 Seville, Spain; (S.G.-G.); (A.R.-L.); (V.M.)
| | - Elena Talero
- Department of Pharmacology, Universidad de Sevilla, 41012 Seville, Spain; (S.G.-G.); (A.R.-L.); (V.M.)
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Iyappan P, Bala M, Sureshkumar M, Veeraraghavan VP, Palanisamy A. Fucoxanthin induced apoptotic cell death in oral squamous carcinoma (KB) cells. Bioinformation 2021; 17:181-191. [PMID: 34393435 PMCID: PMC8340688 DOI: 10.6026/97320630017181] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Revised: 12/31/2020] [Accepted: 01/26/2021] [Indexed: 12/20/2022] Open
Abstract
Fucoxanthin (Fx) is an active compound commonly found in the many types of seaweed with numerous biological activities. The main goal of this investigation is to explore the effect of Fx against the cell proliferation, apoptotic induction and oxidative stress in the oral squamous (KB) cell line. Cytotoxicity of Fx was determined by MTT assay. The intracellular ROS production, mitochondrial membrane potential (MMP) and apoptosis induction in KB cells were examined through DCFH-DA, Rhodamine-123 and DAPI, and dual staining techniques. Effect of Fx on the antioxidant enzymes and lipid peroxidation in the KB cells was studied through the standard procedures. Fx treated KB cells showed morphological changes and reduced cell survival, which is exhibited by the cytotoxic activity of 50 µM/ml (IC50) Fx against the KB cells. The Fx treatment considerably induced the apoptotosis cells (EB/AO) and decreased the MMP (Rh-123) in KB cells. Further, it was pointed out that there was an increased lipid peroxidation (LPO) with decreased antioxidants (CAT, SOD and GSH). These results concluded that Fx has the cytotoxic effect against KB cells and has the potential to induce the apoptosis via increased oxidative stress. Hence, the Fx can be a promising agent for the treatment of oral cancer and it may lead to the development of cancer therapeutics.
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Affiliation(s)
- Petchi Iyappan
- Senior Lecturer, Faculty of Medicine, Bioscience and Nursing, School of Bioscience, Mahsa University, Saujana Putra Campus, Jalan SP2, Bandar Saujana Putra, 42610, Jenjarom, Selangor, Malaysia
| | - M.Devi Bala
- Research Scholar, Muthayammal College of Arts & Science (A Unit of VANETRA Group), Rasipuram, 637408, Namakkal, Tamilnadu, India
| | - M Sureshkumar
- Department of Zoology & Biotechnology, Muthayammal College of Arts & Science (A Unit of VANETRA Group), Rasipuram, 637408, Namakkal, Tamilnadu, India
| | - Vishnu Priya Veeraraghavan
- Department of Biochemistry, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai - 600 077
| | - Arulselvan Palanisamy
- Adjunct Associate Professor,Muthayammal Centre for Advanced Research (MCAR), Muthayammal College of Arts & Science (A Unit of VANETRA Group),Rasipuram, 637408, Namakkal, Tamilnadu, India
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11
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Ming JX, Wang ZC, Huang Y, Ohishi H, Wu RJ, Shao Y, Wang H, Qin MY, Wu ZL, Li YY, Chang Zhou S, Chen H, Liu H, Xu R. Fucoxanthin extracted from Laminaria Japonica inhibits metastasis and enhances the sensitivity of lung cancer to Gefitinib. JOURNAL OF ETHNOPHARMACOLOGY 2021; 265:113302. [PMID: 32860893 DOI: 10.1016/j.jep.2020.113302] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/09/2020] [Revised: 08/04/2020] [Accepted: 08/21/2020] [Indexed: 06/11/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Laminaria japonica, a brown seaweed, has been used in Traditional Chinese Medicine (TCM) to treat a variety of diseases including lung cancer. AIM OF THE STUDY To demonstrate the effects of Fucoxanthin (FX), a major active component extracted from Laminaria japonica on metastasis and Gefitinib (Gef) sensitivity in human lung cancer cells both in vitro and in vivo. MATERIALS AND METHODS Invasion and migration of lung cancer cells were detected using the wound healing assay and transwell assay. Epithelial-to-mesenchymal transition (EMT) factors and PI3K/AKT/NF-κB pathways were analyzed by western blotting. RNA interference (RNAi) technology was used to silence TIMP-2 gene expression in A549 cells. The anti-metastatic effect of FX was evaluated in vivo in an experimental lung metastatic tumor model. On the other hand, cell counting kit-8 assay was used to study the cell viability of human lung cancer PC9 cells and Gef resistant PC9 cells (PC9/G) after Gef, FX or FX combined with Gef treatment. PC9 xenograft model was established to explore the anti-tumor effect of FX or combined with Gef. Immunohistochemistry staining assay and immunofluorescence staining assay were used to reveal the effects of FX on lung cancer cell proliferation and apoptosis. RESULTS FX was able to significantly inhibit lung cancer cells migration and invasion in vitro. FX suppressed the expressions of Snail, Twist, Fibronectin, N-cadherin, MMP-2, PI3K, p-AKT and NF-κB, and increased the expression of TIMP-2. Furthermore, knockdown of TIMP-2 attenuated FX-mediated invasion inhibition. Additionally, we demonstrated that FX inhibited lung cancer cells metastasis in vivo. The anti-metastatic effects of FX on lung cancer cells might be attributed to inhibition of EMT and PI3K/AKT/NF-κB pathway. We further demonstrated that the anti-tumor activity of FX was not only limited to the drug sensitive cell lines, but also prominent on lung cancer cells with Gef resistant phenotype. Furthermore, in vivo xenograft assay confirmed that FX inhibited tumor growth and enhanced the sensitivity of lung cancer cells to Gef and this effect may be due to inhibition of tumor cell proliferation and activation of apoptosis. CONCLUSION Collectively, our findings suggested that FX suppresses metastasis of lung cancer cells and overcomes EGFR TKIs resistance. Thus, FX is worthy of further investigation as a drug candidate for the treatment of lung cancer.
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Affiliation(s)
- Jia Xiong Ming
- Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Zhao Cong Wang
- Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Yi Huang
- Biomedical Analysis Center, Army Medical University, Chongqing, 400038, China
| | | | - Rong Ji Wu
- Eiho Technology (WUHAN) Co., Ltd., Wuhan, 430030, China
| | - Yan Shao
- Biomedical Analysis Center, Army Medical University, Chongqing, 400038, China
| | - Hui Wang
- Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Ming Yang Qin
- Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Ze Liang Wu
- Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Yi Yong Li
- Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Shun Chang Zhou
- Center of Experimental Animals, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Hui Chen
- Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; The Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation of Hubei Province, Wuhan, 430030, China
| | - Hui Liu
- Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; The Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation of Hubei Province, Wuhan, 430030, China
| | - Rong Xu
- Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; The Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation of Hubei Province, Wuhan, 430030, China.
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12
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Splicing Genomics Events in Cervical Cancer: Insights for Phenotypic Stratification and Biomarker Potency. Genes (Basel) 2021; 12:genes12020130. [PMID: 33498485 PMCID: PMC7909518 DOI: 10.3390/genes12020130] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Revised: 01/09/2021] [Accepted: 01/12/2021] [Indexed: 12/24/2022] Open
Abstract
Gynaecological cancers are attributed to the second most diagnosed cancers in women after breast cancer. On a global scale, cervical cancer is the fourth most common cancer and the most common cancer in developing countries with rapidly increasing mortality rates. Human papillomavirus (HPV) infection is a major contributor to the disease. HPV infections cause prominent cellular changes including alternative splicing to drive malignant transformation. A fundamental characteristic attributed to cancer is the dysregulation of cellular transcription. Alternative splicing is regulated by several splicing factors and molecular changes in these factors lead to cancer mechanisms such as tumour development and progression and drug resistance. The serine/arginine-rich (SR) proteins and heterogeneous ribonucleoproteins (hnRNPs) have prominent roles in modulating alternative splicing. Evidence shows molecular alteration and expression levels in these splicing factors in cervical cancer. Furthermore, aberrant splicing events in cancer-related genes lead to chemo- and radioresistance. Identifying clinically relevant modifications in alternative splicing events and splicing variants, in cervical cancer, as potential biomarkers for their role in cancer progression and therapy resistance is scrutinised. This review will focus on the molecular mechanisms underlying the aberrant splicing events in cervical cancer that may serve as potential biomarkers for diagnosis, prognosis, and novel drug targets.
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Moga MA, Dima L, Balan A, Blidaru A, Dimienescu OG, Podasca C, Toma S. Are Bioactive Molecules from Seaweeds a Novel and Challenging Option for the Prevention of HPV Infection and Cervical Cancer Therapy?-A Review. Int J Mol Sci 2021; 22:E629. [PMID: 33435168 PMCID: PMC7826946 DOI: 10.3390/ijms22020629] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Revised: 01/05/2021] [Accepted: 01/07/2021] [Indexed: 12/11/2022] Open
Abstract
Cervical cancer represents one of the leading causes of cancer-related death in women all over the world. The infection with human papilloma virus (HPV) is one of the major risk factors for the development of premalignant lesions, which will progress to cervical cancer. Seaweeds are marine organisms with increased contents of bioactive compounds, which are described as potential anti-HPV and anti-cervical cancer agents. Our study aims to bring together all the results of the previous studies, conducted in order to highlight the potency of bioactive molecules from seaweeds, as anti-HPV and anti-cervical agents. This paper is a review of the English literature published between January 2010 and August 2020. We performed a systematic study in the Google Academic and PubMed databases using the key words "HPV infection", "anticancer", "seaweeds", "cervical cancer" and "carcinogenesis process", aiming to evaluate the effects of different bioactive molecules from marine algae on cervical cancer cell lines and on HPV-infected cells. Only original studies were considered for our research. None of the papers was excluded due to language usage or affiliation. Recent discoveries pointed out that sulfated polysaccharides, such as dextran sulfate heparan or cellulose sulfate, blocked the ability of HPV to infect cells, and inhibited the carcinogenesis process. Carrageenans inhibited the virions of HPV from binding the cellular wall. Fucoidan induced the growth inhibition of HeLa cervical cells in vitro. Heterofucans exhibited antiproliferative effects on cancer cell lines. Terpenoids from brown algae are also promising agents with anti-cervical cancer activity. Considering all the results of the previous studies, we observed that great amounts of bioactive molecules from seaweeds could treat both unapparent HPV infection and clinical visible disease. Furthermore, these molecules were very efficient in the treatment of invasive cervical carcinomas. In these conditions, we consider seaweeds extracts as a novel and challenging therapeutic strategy, and we hope that our study paves the way for further clinical trials in the field.
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Affiliation(s)
- Marius Alexandru Moga
- Department of Medical and Surgical Specialties, Faculty of Medicine, Transylvania University of Brasov, 500019 Brasov, Romania; (M.A.M.); (O.G.D.); (C.P.)
| | - Lorena Dima
- Department of Fundamental, Prophylactic and Clinical Sciences, Faculty of Medicine, University Transilvania of Brasov, 500019 Brasov, Romania; (L.D.); (S.T.)
| | - Andreea Balan
- Department of Medical and Surgical Specialties, Faculty of Medicine, Transylvania University of Brasov, 500019 Brasov, Romania; (M.A.M.); (O.G.D.); (C.P.)
| | - Alexandru Blidaru
- Department of Surgical Oncology, Oncological Institute “Al. Trestioneanu” of Bucharest, University of Medicine and Pharmacy Carol Davila Bucharest, 020021 Bucharest, Romania
| | - Oana Gabriela Dimienescu
- Department of Medical and Surgical Specialties, Faculty of Medicine, Transylvania University of Brasov, 500019 Brasov, Romania; (M.A.M.); (O.G.D.); (C.P.)
| | - Cezar Podasca
- Department of Medical and Surgical Specialties, Faculty of Medicine, Transylvania University of Brasov, 500019 Brasov, Romania; (M.A.M.); (O.G.D.); (C.P.)
| | - Sebastian Toma
- Department of Fundamental, Prophylactic and Clinical Sciences, Faculty of Medicine, University Transilvania of Brasov, 500019 Brasov, Romania; (L.D.); (S.T.)
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Fucoxanthin, a Marine-Derived Carotenoid from Brown Seaweeds and Microalgae: A Promising Bioactive Compound for Cancer Therapy. Int J Mol Sci 2020; 21:ijms21239273. [PMID: 33291743 PMCID: PMC7730715 DOI: 10.3390/ijms21239273] [Citation(s) in RCA: 85] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Revised: 12/01/2020] [Accepted: 12/02/2020] [Indexed: 12/15/2022] Open
Abstract
Fucoxanthin is a well-known carotenoid of the xanthophyll family, mainly produced by marine organisms such as the macroalgae of the fucus genus or microalgae such as Phaeodactylum tricornutum. Fucoxanthin has antioxidant and anti-inflammatory properties but also several anticancer effects. Fucoxanthin induces cell growth arrest, apoptosis, and/or autophagy in several cancer cell lines as well as in animal models of cancer. Fucoxanthin treatment leads to the inhibition of metastasis-related migration, invasion, epithelial–mesenchymal transition, and angiogenesis. Fucoxanthin also affects the DNA repair pathways, which could be involved in the resistance phenotype of tumor cells. Moreover, combined treatments of fucoxanthin, or its metabolite fucoxanthinol, with usual anticancer treatments can support conventional therapeutic strategies by reducing drug resistance. This review focuses on the current knowledge of fucoxanthin with its potential anticancer properties, showing that fucoxanthin could be a promising compound for cancer therapy by acting on most of the classical hallmarks of tumor cells.
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15
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Protein kinases as targets for developing anticancer agents from marine organisms. Biochim Biophys Acta Gen Subj 2020; 1865:129759. [PMID: 33038451 DOI: 10.1016/j.bbagen.2020.129759] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Revised: 09/03/2020] [Accepted: 10/03/2020] [Indexed: 01/11/2023]
Abstract
Protein kinases play a fundamental role in the intracellular transduction because of their ability to phosphorylate plethora of proteins. Over the past three decades, numerous protein kinase inhibitors have been identified and are being used clinically successfully. The biodiversity of marine organisms provides a rich source for the discovery and development of novel anticancer agents in the treatment of human malignancies and a lot of bioactive ingredients from marine organisms display anticancer effects by affecting the protein kinases-mediated pathways. In the present mini-review, anticancer compounds from marine source were reviewed and discussed in context of their targeted pathways associated with protein kinases and the progress of these compounds as anticancer agents in recent five years were emphasized. The molecular entities and their modes of actions were presented. We focused on protein kinases-mediated signaling pathways including PI3K/Akt/mTOR, p38 MAPK, and EGFR. The marine compounds targeting special pathways of protein kinases were highlighted. We have also discussed the existing challenges and prospects related to design and development of novel protein kinase inhibitors from marine sources.
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Padilla-Raygoza N, Monroy-Torres R, Sandoval-Salazar C, Vera-Becerra LE, Patiño-López ME, de Lourdes García-Campos M, Campos VB, del Carmen Ortega Jiménez M, del Carmen Delgado-Sandoval S, Ramírez-Gómez XS, Jimenez-García SN, Lemus HLL. Cancer prevention programmes in Mexico: are we doing enough? Ecancermedicalscience 2020; 14:997. [PMID: 32153652 PMCID: PMC7032937 DOI: 10.3332/ecancer.2020.997] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2019] [Indexed: 12/20/2022] Open
Abstract
Cancer has increased in all the countries of the world and Mexico is no exception. The recognised risk factors for the main types of cancer are reviewed and searched through the Mexican government web pages and cancer prevention programmes to tackle the risk factors in the population. The Mexican government, a member of the World Health Organization, shows that the main approach is an early diagnosis rather than prevention, forgetting that an ounce of prevention is better than a pound of cure. Effective public programmes should be promoted to reduce preventable risk factors in the population (smoking, nutrition, obesity, diet, environmental toxicity, sedentary lifestyle) and control the non-preventable factors (genetics) if we really want to control the incidence of different types of cancer.
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Affiliation(s)
| | - Rebeca Monroy-Torres
- Laboratory of Nutrition and Safety Food, Department of Medicine and Nutrition, Division of Health Sciences, Campus Leon, University of Guanajuato, León CP 37670, Mexico
| | - Cuauhtémoc Sandoval-Salazar
- Department of Nursing and Obstetrics, Division of Health Sciences, Campus Celaya-Salvatierra, University of Guanajuato, Celaya CP38110, Mexico
| | - Luz Elvia Vera-Becerra
- Department of Medicine and Nutrition, Division of Health Sciences, Campus Leon, University of Guanajuato, León CP 37670, Mexico
| | - María Esther Patiño-López
- Department of Clinical Nursing, Division of Health Sciences, Campus Celaya-Salvatierra, University of Guanajuato, Celaya CP38110, Mexico
| | - María de Lourdes García-Campos
- Department of Clinical Nursing, Division of Health Sciences, Campus Celaya-Salvatierra, University of Guanajuato, Celaya CP38110, Mexico
| | - Vicente Beltrán Campos
- Department of Clinical Nursing, Division of Health Sciences, Campus Celaya-Salvatierra, University of Guanajuato, Celaya CP38110, Mexico
| | - Mayra del Carmen Ortega Jiménez
- Department of Nursing and Obstetrics, Division of Health Sciences, Campus Celaya-Salvatierra, University of Guanajuato, Celaya CP38110, Mexico
| | - Silvia del Carmen Delgado-Sandoval
- Department of Nursing and Obstetrics, Division of Health Sciences, Campus Celaya-Salvatierra, University of Guanajuato, Celaya CP38110, Mexico
| | - Xóchitl Sofía Ramírez-Gómez
- Department of Clinical Nursing, Division of Health Sciences, Campus Celaya-Salvatierra, University of Guanajuato, Celaya CP38110, Mexico
| | - Sandra Neli Jimenez-García
- Department of Clinical Nursing, Division of Health Sciences, Campus Celaya-Salvatierra, University of Guanajuato, Celaya CP38110, Mexico
| | - Hilda Lissette López- Lemus
- Department of Nursing and Obstetrics, Division of Health Sciences, Campus Celaya-Salvatierra, University of Guanajuato, Celaya CP38110, Mexico
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A critical review on anti-angiogenic property of phytochemicals. J Nutr Biochem 2019; 71:1-15. [PMID: 31174052 DOI: 10.1016/j.jnutbio.2019.04.006] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2019] [Revised: 04/12/2019] [Accepted: 04/25/2019] [Indexed: 12/14/2022]
Abstract
Angiogenesis, a process involved in neovascularization, has been found to be associated with several metabolic diseases like cancer, retinopathy etc. Thus, currently, the focus on anti-angiogenic therapy for treatment and prevention of diseases has gained significant attention. Currently available Food and Drug Administration (FDA) approved drugs are targeting either vascular endothelial growth factor or it's receptor, but in the long term, these approaches were shown to cause several side effects and the chances of developing resistance to these drugs is also high. Therefore, identification of safe and cost-effective anti-angiogenic molecules is highly imperative. Over the past decades, dietary based natural compounds have been studied for their anti-angiogenic potential which provided avenues in improving the angiogenesis based therapy. In this review, major emphasis is given to the molecular mechanism behind anti-angiogenic effect of natural compounds from dietary sources.
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Ercolano G, De Cicco P, Ianaro A. New Drugs from the Sea: Pro-Apoptotic Activity of Sponges and Algae Derived Compounds. Mar Drugs 2019; 17:E31. [PMID: 30621025 PMCID: PMC6356258 DOI: 10.3390/md17010031] [Citation(s) in RCA: 48] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2018] [Revised: 12/21/2018] [Accepted: 12/28/2018] [Indexed: 12/12/2022] Open
Abstract
Natural compounds derived from marine organisms exhibit a wide variety of biological activities. Over the last decades, a great interest has been focused on the anti-tumour role of sponges and algae that constitute the major source of these bioactive metabolites. A substantial number of chemically different structures from different species have demonstrated inhibition of tumour growth and progression by inducing apoptosis in several types of human cancer. The molecular mechanisms by which marine natural products activate apoptosis mainly include (1) a dysregulation of the mitochondrial pathway; (2) the activation of caspases; and/or (3) increase of death signals through transmembrane death receptors. This great variety of mechanisms of action may help to overcome the multitude of resistances exhibited by different tumour specimens. Therefore, products from marine organisms and their synthetic derivates might represent promising sources for new anticancer drugs, both as single agents or as co-adjuvants with other chemotherapeutics. This review will focus on some selected bioactive molecules from sponges and algae with pro-apoptotic potential in tumour cells.
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Affiliation(s)
- Giuseppe Ercolano
- Department of Pharmacy, School of Medicine, University of Naples Federico II, 80131 Naples, Italy.
| | - Paola De Cicco
- Department of Pharmacy, School of Medicine, University of Naples Federico II, 80131 Naples, Italy.
| | - Angela Ianaro
- Department of Pharmacy, School of Medicine, University of Naples Federico II, 80131 Naples, Italy.
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Ren CC, Yang L, Liu L, Chen YN, Cheng GM, Zhang XA, Liu H. Effects of shRNA-mediated silencing of PSMA7 on cell proliferation and vascular endothelial growth factor expression via the ubiquitin-proteasome pathway in cervical cancer. J Cell Physiol 2018; 234:5851-5862. [PMID: 29247526 DOI: 10.1002/jcp.26408] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2017] [Revised: 10/11/2017] [Indexed: 12/20/2022]
Abstract
This study aims to evaluate the effects of PSMA7 silencing on cervical cancer (CC) cell proliferation and vascular endothelial growth factor (VEGF) expression through the ubiquitin-proteasome pathway. CC tissues (n = 43) and normal tissues (n = 27) were first collected from patients. Human CC cell line (SiHa) and human normal cervical epithelial cells (H8) were obtained and classified into the normal, blank, negative control (NC), PSMA7-shRNA1, and PSMA7-shRNA2 groups, respectively. In situ hybridization was used to detect the expressions of wild-type and mutant p53 proteins. Immunofluorescence assay was carried out to test the activity of 20S proteasomes. Reverse transcription quantitative polymerase chain reaction and Western blot analysis were both performed to determine the expressions of PSMA7, ubiquitin, P27, P53, and VEGF in sample tissues and cells. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay was used to analyze cell proliferation rates, and flow cytometry was used to analyze the cell cycle and the apoptotic rate. Compared with normal tissues, CC tissues showed increased expression levels of PSMA7, ubiquitin, p53, VEGF as well as increased activity of 20S proteasomes but exhibited a decrease in p27 expression. Compared with the blank and NC groups, the PSMA7-shRNA1 and PSMA7-shRNA2 groups all had decreased expression levels of PSMA7, ubiquitin, p53, and VEGF as well as decreased cell proliferation, 20S proteasomes activity, and cell number in the S phase, increased p27 expression, cell apoptosis and cell number in the G0/G1 phase. Our study demonstrated that PSMA7 silencing can suppress CC cell proliferation and VEGF expression in addition to promoting cell apoptosis through inhibiting the UPP signaling pathway.
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Affiliation(s)
- Chen-Chen Ren
- Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Li Yang
- Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Ling Liu
- Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yan-Nan Chen
- Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Guo-Mei Cheng
- Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Xiao-An Zhang
- Department of Imaging, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Hui Liu
- Department of Oncology, The First Affiliated Hospital of Kunming Medical University, Kunming, China
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Foo SC, Yusoff FM, Imam MU, Foo JB, Ismail N, Azmi NH, Tor YS, Khong NMH, Ismail M. Increased fucoxanthin in Chaetoceros calcitrans extract exacerbates apoptosis in liver cancer cells via multiple targeted cellular pathways. ACTA ACUST UNITED AC 2018; 21:e00296. [PMID: 30581767 PMCID: PMC6296166 DOI: 10.1016/j.btre.2018.e00296] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2018] [Revised: 11/14/2018] [Accepted: 12/03/2018] [Indexed: 02/08/2023]
Abstract
Both treatments inhibited cancer proliferation in a time and dose dependent manner. FxRF treatment were effective in inducing apoptosis in HepG2 cells than crude extract. Treatments stimulated regulation in cell signalling, apoptotic and antioxidant genes. In this study, anti-proliferative effects of C. calcitrans extract and its fucoxanthin rich fraction (FxRF) were assessed on human liver HepG2 cancer cell line. Efficacy from each extract was determined by cytotoxicity assay, morphological observation, and cell cycle analysis. Mechanisms of action observed were evaluated using multiplex gene expression analysis. Results showed that CME and FxRF induced cytotoxicity to HepG2 cells in a dose and time-dependent manner. FxRF (IC50: 18.89 μg.mL−1) was found to be significantly more potent than CME (IC50: 87.5 μg.mL−1) (p < 0.05). Gene expression studies revealed that anti-proliferative effects in treated cells by C. calcitrans extracts were mediated partly through the modulation of numerous genes involved in cell signaling (AKT1, ERK1/2, JNK), apoptosis (BAX, BID, Bcl-2, APAF, CYCS) and oxidative stress (SOD1, SOD2, CAT). Overall, C. calcitrans extracts demonstrated effective intervention against HepG2 cancer cells where enhanced apoptotic activities were observed with increased fucoxanthin content.
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Affiliation(s)
- Su Chern Foo
- Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor Darul Ehsan, Malaysia.,School of Science, Monash University Malaysia, Jalan Lagoon Selatan, 47500, Bandar Sunway, Selangor Darul Ehsan, Malaysia
| | - Fatimah Md Yusoff
- Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor Darul Ehsan, Malaysia.,The International Institute of Aquaculture and Aquatic Science, Universiti Putra Malaysia, 43400, UPM, Serdang, Selangor Darul Ehsan, Malaysia.,Department of Aquaculture, Faculty of Agriculture, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor Darul Ehsan, Malaysia
| | - Mustapha Umar Imam
- Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor Darul Ehsan, Malaysia.,Department of Medical Biochemistry, College of Health Sciences, Usmanu Danfodio University, Sokoto, Nigeria
| | - Jhi Biau Foo
- Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor Darul Ehsan, Malaysia.,School of Pharmacy, Faculty of Health & Medical Sciences, Taylor's University, No. 1 Jalan Taylor's, 47500, Subang Jaya, Selangor Darul Ehsan, Malaysia
| | - Norsharina Ismail
- Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor Darul Ehsan, Malaysia
| | - Nur Hanisah Azmi
- Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor Darul Ehsan, Malaysia.,Department of Cell and Molecular Biology, Faculty of Biotechnology & Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor, Malaysia
| | - Yin Sim Tor
- Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor Darul Ehsan, Malaysia.,School of Biosciences, Faculty of Health & Medical Sciences, Taylor's University, No. 1 Jalan Taylor's, 47500, Subang Jaya, Selangor Darul Ehsan, Malaysia
| | - Nicholas M H Khong
- Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor Darul Ehsan, Malaysia
| | - Maznah Ismail
- Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor Darul Ehsan, Malaysia
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21
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Zhu Y, Cheng J, Min Z, Yin T, Zhang R, Zhang W, Hu L, Cui Z, Gao C, Xu S, Zhang C, Hu X. Effects of fucoxanthin on autophagy and apoptosis in SGC-7901cells and the mechanism. J Cell Biochem 2018; 119:7274-7284. [PMID: 29761894 DOI: 10.1002/jcb.27022] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2017] [Accepted: 04/05/2018] [Indexed: 01/20/2023]
Abstract
Autophagy and apoptosis are involved in the development of a variety of cancers. Fucoxanthin is a natural compound known to have antitumor effects, so we aimed to explore its effects on autophagy and apoptosis in gastric cancer SGC7901 cells. Specifically, we performed methyl thiazolyl tetrazolium assay, transmission electron microscopy, real-time polymerase chain reaction, Western blot analysis, immunofluorescence assay, and cell apoptosis analysis to clarify the role of fucoxanthin in SGC-7901 cells. Our results indicate that fucoxanthin significantly inhibits the viability of SGC-7901 cells, effectively inducing both autophagy and apoptosis by up-regulating the expressions of beclin-1, LC3, and cleaved caspase-3 (CC3), and by down regulating Bcl-2. Fucoxanthin-induced autophagy also seems to occur before, and may promote apoptosis.
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Affiliation(s)
- Yue Zhu
- Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Wuhan University of Science and technology, Wuhan, Hubei, China
- Department of Biomedical Engineering, School of Medicine and School of Engineering, The University of Alabama at Birmingham, Birmingham, Alabama
| | - Jing Cheng
- Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Wuhan University of Science and technology, Wuhan, Hubei, China
- Department of Biomedical Engineering, School of Medicine and School of Engineering, The University of Alabama at Birmingham, Birmingham, Alabama
| | - Zhenli Min
- Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Wuhan University of Science and technology, Wuhan, Hubei, China
- Department of Biomedical Engineering, School of Medicine and School of Engineering, The University of Alabama at Birmingham, Birmingham, Alabama
| | - Tingzi Yin
- Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Wuhan University of Science and technology, Wuhan, Hubei, China
- Department of Biomedical Engineering, School of Medicine and School of Engineering, The University of Alabama at Birmingham, Birmingham, Alabama
| | - Rong Zhang
- Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Wuhan University of Science and technology, Wuhan, Hubei, China
- Department of Biomedical Engineering, School of Medicine and School of Engineering, The University of Alabama at Birmingham, Birmingham, Alabama
| | - Wei Zhang
- Department of Rehabilitation Medicine, China Resources & WISCO General Hospital, Wuhan, Hubei, China
| | - Ling Hu
- Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Wuhan University of Science and technology, Wuhan, Hubei, China
- Department of Biomedical Engineering, School of Medicine and School of Engineering, The University of Alabama at Birmingham, Birmingham, Alabama
| | - Zhiwen Cui
- Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Wuhan University of Science and technology, Wuhan, Hubei, China
- Department of Biomedical Engineering, School of Medicine and School of Engineering, The University of Alabama at Birmingham, Birmingham, Alabama
| | - Chengzhi Gao
- Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Wuhan University of Science and technology, Wuhan, Hubei, China
- Department of Biomedical Engineering, School of Medicine and School of Engineering, The University of Alabama at Birmingham, Birmingham, Alabama
| | - Shiqiang Xu
- Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Wuhan University of Science and technology, Wuhan, Hubei, China
| | - Chunxiang Zhang
- Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Wuhan University of Science and technology, Wuhan, Hubei, China
- Department of Biomedical Engineering, School of Medicine and School of Engineering, The University of Alabama at Birmingham, Birmingham, Alabama
| | - Xiamin Hu
- Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Wuhan University of Science and technology, Wuhan, Hubei, China
- Department of Pharmacy, Shanghai University of Medicine & Health Sciences, Shanghai, China
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22
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Liu Q, Liang X, Niu C, Wang X. Ellagic acid promotes A549 cell apoptosis via regulating the phosphoinositide 3-kinase/protein kinase B pathway. Exp Ther Med 2018; 16:347-352. [PMID: 29896260 PMCID: PMC5995078 DOI: 10.3892/etm.2018.6193] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2017] [Accepted: 03/01/2018] [Indexed: 01/03/2023] Open
Abstract
The present study aimed to evaluate the anti-cancer effect of ellagic acid in human non-small cell lung cancer (NSCLC) A549 cells and to reveal the potential underlying mechanism. The effects of ellagic acid on the cell proliferation of A549 cells were determined by MTT assay. Cell cycle and apoptosis were measured with flow cytometry and Annexin V-propidium iodide staining. Western blotting was used to measure the expression levels of the phosphatidylinositol 3-kinase (PI3K)/protein kinas B (Akt) signaling pathway and apoptosis-associated proteins. It was demonstrated that ellagic acid exerted an inhibitory effect in the proliferation of human NSCLC A549 cells. Flow cytometry demonstrated that G1 phase retention and apoptosis rates were significantly increased after treatment with ellagic acid. Further investigation revealed that ellagic acid treatment diminished the phosphorylation of PI3K and Akt and regulated the expression of apoptosis-associated proteins in A549 cells. In conclusion, the present results indicated that ellagic acid suppresses cell proliferation, arrests cell cycle and induces apoptosis in human NSCLC A549 cells by inhibiting the PI3K/Akt signaling pathway.
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Affiliation(s)
- Qiong Liu
- Medical Experiment Center, Xinhua College of Sun Yat-sen University, Guangzhou, Guangdong 510520, P.R. China
| | - Xiaobing Liang
- Medical Experiment Center, Xinhua College of Sun Yat-sen University, Guangzhou, Guangdong 510520, P.R. China
| | - Chengwei Niu
- Medical Experiment Center, Xinhua College of Sun Yat-sen University, Guangzhou, Guangdong 510520, P.R. China
| | - Xuelan Wang
- Medical Experiment Center, Xinhua College of Sun Yat-sen University, Guangzhou, Guangdong 510520, P.R. China
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23
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Ravi H, Kurrey N, Manabe Y, Sugawara T, Baskaran V. Polymeric chitosan-glycolipid nanocarriers for an effective delivery of marine carotenoid fucoxanthin for induction of apoptosis in human colon cancer cells (Caco-2 cells). MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2018; 91:785-795. [PMID: 30033314 DOI: 10.1016/j.msec.2018.06.018] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/04/2017] [Revised: 05/25/2018] [Accepted: 06/09/2018] [Indexed: 01/25/2023]
Abstract
Fucoxanthin (FUCO), a marine carotenoid is photo-, and thermo-labile and poorly bioavailable due to its lipophilicity. Hence, we developed a chitosan (CS) + glycolipid (GL) nanogels (NGs) to increase cellular uptake and anticancer efficacy of FUCO (10 μM) in human colon cells (Caco-2). Effect of FUCO loaded in NGs with/with no GL was studied in comparison with micellar FUCO. Results showed that the cell viability was lower (p < 0.05) in NGs + GL (50.5%) compared to NGs (-GL) (66.5%) and the mixed micelles (72.5%) groups over 48 h exposure. An enhanced reactive oxygen species (ROS) generation was evident in NGs + GL (379.2%) group compared to NGs (-GL) and mixed micelles groups. Further, induction of apoptosis with an increased chromatin condensation and DNA fragmentation as evidenced in DAPI staining and DNA ladder assay were higher in NGs + GL group than other groups. Down-regulation of Bcl-2 (6.6 folds) was higher in NGs + GL group compared to NGs (-GL) (1.94 fold) and mixed micelles (1.19 fold) groups. Higher Bax up-regulation in NGs + GL compared to other groups supports the Bcl-2 down regulation. Mitochondrial membrane polarisation (ΔΨm) was higher in NGs + GL group (2.46 fold) compared to NGs (-GL) (1.91 fold) and mixed micelles (1.26 fold) groups. The cellular FUCO uptake illustrated a positive correlation between its level (pmol/106 cells) in NGs + GL (758.3) and enhanced caspase-3 activity (25.8 folds). This could be the reason for an increased apoptotic activity in NGs + GL group than other groups. Results demonstrate that delivery of FUCO in NGs + GL carrier aids cellular uptake and chemotherapeutic potential of FUCO. Results further demonstrate, for the first time, higher anti-cancer activity of FUCO loaded in NGs + GL and the effect was through ROS generation via a caspase dependent mechanism in Caco-2 cells.
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Affiliation(s)
- Hindupur Ravi
- Department of Biochemistry, CSIR-Central Food Technological Research Institute, Mysuru-570020, Karnataka, India
| | - Nawneet Kurrey
- Department of Biochemistry, CSIR-Central Food Technological Research Institute, Mysuru-570020, Karnataka, India
| | - Yuki Manabe
- Department of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan
| | - Tatsuya Sugawara
- Department of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan
| | - Vallikannan Baskaran
- Department of Biochemistry, CSIR-Central Food Technological Research Institute, Mysuru-570020, Karnataka, India.
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24
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Jin Y, Qiu S, Shao N, Zheng J. Fucoxanthin and Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) Synergistically Promotes Apoptosis of Human Cervical Cancer Cells by Targeting PI3K/Akt/NF-κB Signaling Pathway. Med Sci Monit 2018; 24:11-18. [PMID: 29291370 PMCID: PMC5759513 DOI: 10.12659/msm.905360] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Background Fucoxanthin is a carotenoid present in the chloroplasts of brown seaweeds. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytokine that selectively induces apoptosis in many tumor cells and is an attractive candidate for antitumor therapies. Material/Methods After human cervical cancer cell lines HeLa, SiHa, and CaSki were treated with fucoxanthin or TRAIL. Cell viability was determined by 2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-2-tetrazolium 5-carboxanilide (XTT) method. Apoptosis was measured by flow cytometry (FCM). Protein expression of phosphatidylinositol 3 kinase (PI3K), protein kinase B (Akt), phosphated Akt (p-Akt), NF-κB nuclear factor-k-gene binding (NF-κB). Phosphated nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (p-IκBa), was measured by Western blot analysis. mRNA expression of Bax and Bcl2 was measured by RNA preparation and quantitative reverse transcription polymerase chain reaction (RT-PCR). Results In the present study, the effectiveness in terms of apoptosis was as follows: TRAIL plus fucoxanthin>fucoxanthin>TRAIL, indicating the combination of fucoxanthin and TRAIL, produced a strong synergistic effect on apoptosis in human cervical cancer cells. Additionally, we found that upstream signaling PI3K/Akt and NF-κB pathways-mediated cell apoptosis was activated by TRAIL and suppressed by fucoxanthin. By using PI3K and NF-κB inhibitors LY49002 and PDTC, we found that fucoxanthin- or TRAIL-induced apoptosis of human cervical cancer cells was obviously down-regulated. Conclusions Taken together, these findings suggest that fucoxanthin and TRAIL increased the apoptosis in human cervical cancer cells by targeting the PI3K/Akt/NF-κB signaling pathway.
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Affiliation(s)
- Ye Jin
- Department of Gynecology and Obstetrics, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China (mainland)
| | - Shuang Qiu
- Department of Gynecology and Obstetrics, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China (mainland)
| | - Na Shao
- Department of Gynecology and Obstetrics, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China (mainland)
| | - Jianhua Zheng
- Department of Gynecology and Obstetrics, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China (mainland)
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25
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Mei C, Zhou S, Zhu L, Ming J, Zeng F, Xu R. Antitumor Effects of Laminaria Extract Fucoxanthin on Lung Cancer. Mar Drugs 2017; 15:E39. [PMID: 28212270 PMCID: PMC5334619 DOI: 10.3390/md15020039] [Citation(s) in RCA: 62] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2016] [Revised: 01/26/2017] [Accepted: 01/28/2017] [Indexed: 12/26/2022] Open
Abstract
Lung cancer is the leading cause of cancer mortality worldwide and non-small-cell lung cancer (NSCLC) is the most common type. Marine plants provide rich resources for anticancer drug discovery. Fucoxanthin (FX), a Laminaria japonica extract, has attracted great research interest for its antitumor activities. Accumulating evidence suggests anti-proliferative effects of FX on many cancer cell lines including NSCLCs, but the detailed mechanisms remain unclear. In the present investigation, we confirmed molecular mechanisms and in vivo anti-lung cancer effect of FX at the first time. Flow cytometry, real-time PCR, western blotting and immunohistochemistry revealed that FX arrested cell cycle and induced apoptosis by modulating expression of p53, p21, Fas, PUMA, Bcl-2 and caspase-3/8. These results show that FX is a potent marine drug for human non-small-cell lung cancer treatment.
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Affiliation(s)
- ChengHan Mei
- Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
| | - ShunChang Zhou
- Department of Laboratory Animal, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
| | - Lin Zhu
- Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
| | - JiaXiong Ming
- Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
| | - FanDian Zeng
- Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
| | - Rong Xu
- Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
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26
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Zhu J, Sun X, Chen X, Wang S, Wang D. Chemical cleavage of fucoxanthin from Undaria pinnatifida and formation of apo-fucoxanthinones and apo-fucoxanthinals identified using LC-DAD-APCI-MS/MS. Food Chem 2016; 211:365-73. [PMID: 27283644 DOI: 10.1016/j.foodchem.2016.05.064] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2015] [Revised: 05/05/2016] [Accepted: 05/11/2016] [Indexed: 01/29/2023]
Abstract
As the most abundant carotenoid in nature, fucoxanthin is susceptible to oxidation under some conditions, forming cleavage products that possibly exhibit both positive and negative health effects in vitro and in vivo. Thus, to produce relatively high amounts of cleavage products, chemical oxidation of fucoxanthin was performed. Kinetic models for oxidation were probed and reaction products were identified. The results indicated that both potassium permanganate (KMnO4) and hypochlorous acid/hypochlorite (HClO/ClO(-)) treatment fitted a first-order kinetic model, while oxidation promoted by hydroxyl radical (OH) followed second-order kinetics. With the help of liquid chromatography-tandem mass spectrometry, a total of 14 apo-fucoxanthins were detected as predominant cleavage products, with structural and geometric isomers identified among them. Three apo-fucoxanthinones and eleven apo-fucoxanthinals, of which five were cis-apo-fucoxanthinals, were detected upon oxidation by the three oxidizing agents (KMnO4, HClO/ClO(-), and OH).
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Affiliation(s)
- Junxiang Zhu
- College of Food Science and Engineering, Ocean University of China, Qingdao 266003, People's Republic of China
| | - Xiaowen Sun
- College of Food Science and Engineering, Ocean University of China, Qingdao 266003, People's Republic of China
| | - Xiaoli Chen
- College of Food Science and Engineering, Ocean University of China, Qingdao 266003, People's Republic of China
| | - Shuhui Wang
- Qingdao Municipal Center for Disease Control & Prevention, Qingdao 266033, People's Republic of China
| | - Dongfeng Wang
- College of Food Science and Engineering, Ocean University of China, Qingdao 266003, People's Republic of China.
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27
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Ji H, Li B, Zhang S, He Z, Zhou Y, Ouyang L. Crk-like adapter protein is overexpressed in cervical carcinoma, facilitates proliferation, invasion and chemoresistance, and regulates Src and Akt signaling. Oncol Lett 2016; 12:3811-3817. [PMID: 27895735 PMCID: PMC5104173 DOI: 10.3892/ol.2016.5160] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2015] [Accepted: 07/01/2016] [Indexed: 12/18/2022] Open
Abstract
Overexpression of Crk-like (CrkL) adapter protein has been implicated in a number of types of human cancer. However, its involvement in human cervical carcinoma remains unclear. The present study aimed to explore the clinical significance and biological characteristics of CrkL in human cervical carcinoma. CrkL protein expression was examined in tissue samples from 92 cases of cervical carcinoma using immunohistochemistry, and was found to be overexpressed in 48.9% (45/92 cases). CrkL was transfected into HeLa and CaSki cervical carcinoma cell lines and its effects on biological behavior were examined. CrkL overexpression was revealed to promote cell proliferation, invasion and chemoresistance. In addition, CrkL overexpression increased the level of Src and Akt phosphorylation. Treatment with the Src inhibitor dasatinib eliminated the effect of CrkL on cell invasion. In conclusion, the current results demonstrate that CrkL is an oncoprotein overexpressed in cervical carcinoma which contributes to malignant cell growth and chemoresistance. In addition, the findings indicate that CrkL promotes cervical cancer cell invasion through a Src-dependent pathway.
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Affiliation(s)
- Hong Ji
- Department of Gynecology and Obstetrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China; Department of Gynecology and Obstetrics, First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121000, P.R. China
| | - Bo Li
- Department of Gynecology and Obstetrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China
| | - Shitai Zhang
- Department of Gynecology and Obstetrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China
| | - Zheng He
- Department of Gynecology and Obstetrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China
| | - Yang Zhou
- Department of Gynecology and Obstetrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China
| | - Ling Ouyang
- Department of Gynecology and Obstetrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China
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28
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Gómez-Loredo A, Benavides J, Rito-Palomares M. Purification and Formulation of Xanthophyll for Pharmaceutical Use: Current Strategies and Future Trends. CHEMBIOENG REVIEWS 2015. [DOI: 10.1002/cben.201500012] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
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29
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Martin LJ. Fucoxanthin and Its Metabolite Fucoxanthinol in Cancer Prevention and Treatment. Mar Drugs 2015; 13:4784-98. [PMID: 26264004 PMCID: PMC4557004 DOI: 10.3390/md13084784] [Citation(s) in RCA: 74] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2015] [Revised: 06/25/2015] [Accepted: 07/27/2015] [Indexed: 01/05/2023] Open
Abstract
Fucoxanthin is a carotenoid present in the chloroplasts of brown seaweeds. When ingested, it is metabolized mainly to fucoxanthinol by digestive enzymes of the gastrointestinal tract. These compounds have been shown to have many beneficial health effects, including anti-mutagenic, anti-diabetic, anti-obesity, anti-inflammatory and anti-neoplastic actions. In every cancer tested, modulatory actions of fucoxanthinol on viability, cell-cycle arrest, apoptosis and members of the NF-κB pathway were more pronounced than that of fucoxanthin. Anti-proliferative and cancer preventing influences of fucoxanthin and fucoxanthinol are mediated through different signalling pathways, including the caspases, Bcl-2 proteins, MAPK, PI3K/Akt, JAK/STAT, AP-1, GADD45, and several other molecules that are involved in cell cycle arrest, apoptosis, anti-angiogenesis or inhibition of metastasis. In this review, we address the mechanisms of action of fucoxanthin and fucoxanthinol according to different types of cancers. Current findings suggest that these compounds could be effective for treatment and/or prevention of cancer development and aggressiveness.
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Affiliation(s)
- Luc J Martin
- Biology Department, Université de Moncton, Moncton, NB E1A 3E9, Canada.
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30
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Geisen U, Zenthoefer M, Peipp M, Kerber J, Plenge J, Managò A, Fuhrmann M, Geyer R, Hennig S, Adam D, Piker L, Rimbach G, Kalthoff H. Molecular Mechanisms by Which a Fucus vesiculosus Extract Mediates Cell Cycle Inhibition and Cell Death in Pancreatic Cancer Cells. Mar Drugs 2015; 13:4470-91. [PMID: 26204945 PMCID: PMC4515628 DOI: 10.3390/md13074470] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2015] [Revised: 07/07/2015] [Accepted: 07/08/2015] [Indexed: 12/14/2022] Open
Abstract
Pancreatic cancer is one of the most aggressive cancer entities, with an extremely poor 5-year survival rate. Therefore, novel therapeutic agents with specific modes of action are urgently needed. Marine organisms represent a promising source to identify new pharmacologically active substances. Secondary metabolites derived from marine algae are of particular interest. The present work describes cellular and molecular mechanisms induced by an HPLC-fractionated, hydrophilic extract derived from the Baltic brown seaweed Fucus vesiculosus (Fv1). Treatment with Fv1 resulted in a strong inhibition of viability in various pancreatic cancer cell lines. This extract inhibited the cell cycle of proliferating cells due to the up-regulation of cell cycle inhibitors, shown on the mRNA (microarray data) and protein level. As a result, cells were dying in a caspase-independent manner. Experiments with non-dividing cells showed that proliferation is a prerequisite for the effectiveness of Fv1. Importantly, Fv1 showed low cytotoxic activity against non-malignant resting T cells and terminally differentiated cells like erythrocytes. Interestingly, accelerated killing effects were observed in combination with inhibitors of autophagy. Our in vitro data suggest that Fv1 may represent a promising new agent that deserves further development towards clinical application.
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Affiliation(s)
- Ulf Geisen
- Division of Molecular Oncology, Institute for Experimental Cancer Research, Medical Faculty, CAU, University Hospital Schleswig-Holstein, 24105 Kiel, Germany.
| | | | - Matthias Peipp
- Division of Stem Cell Transplantation and Immunotherapy, Department of Internal Medicine II, University Hospital Schleswig-Holstein, 24105 Kiel, Germany.
| | - Jannik Kerber
- Division of Molecular Oncology, Institute for Experimental Cancer Research, Medical Faculty, CAU, University Hospital Schleswig-Holstein, 24105 Kiel, Germany.
| | - Johannes Plenge
- Institute of Immunology, University Hospital Schleswig-Holstein, 24105 Kiel, Germany.
| | | | | | | | - Steffen Hennig
- CRM, Coastal Research & Management, 24159 Kiel, Germany.
| | - Dieter Adam
- Institute of Immunology, University Hospital Schleswig-Holstein, 24105 Kiel, Germany.
| | - Levent Piker
- CRM, Coastal Research & Management, 24159 Kiel, Germany.
| | - Gerald Rimbach
- Institute of Human Nutrition and Food Science, Christian-Albrechts University of Kiel, 24118 Kiel, Germany.
| | - Holger Kalthoff
- Division of Molecular Oncology, Institute for Experimental Cancer Research, Medical Faculty, CAU, University Hospital Schleswig-Holstein, 24105 Kiel, Germany.
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Terasaki M, Mutoh M, Fujii G, Takahashi M, Ishigamori R, Masuda S. Potential ability of xanthophylls to prevent obesity-associated cancer. World J Pharmacol 2014; 3:140-152. [DOI: 10.5497/wjp.v3.i4.140] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2014] [Revised: 10/02/2014] [Accepted: 11/03/2014] [Indexed: 02/06/2023] Open
Abstract
Obesity-associated cancers, including colon cancer and breast cancer, are increasing in Asian countries with Westernized lifestyles as exemplified by reduced physical activity and increased fat/sugar consumption. An excessive accumulation of visceral adipose tissue causes insulin resistance, dyslipidemia and adipocytokine imbalance, and these factors are suggested to be involved in cancer promotion. To prevent obesity-associated cancers, researcher attention is increasing on the so-called “functional foods”. In addition, new approaches to cancer control are in high demand, and using “functional foods” as supplemental or adjuvant agents in chemotherapy is thought to be a promising approach. One of these functional ingredients is xanthophylls, which are natural fat-soluble pigments found in fruits, vegetables, algae and other plants. Xanthophylls belong to the carotenoid class and have structures containing oxygen. Some studies have revealed that xanthophylls improve the inflammation status, serum triglyceride levels, blood pressure levels and liver function test values. Furthermore, recent studies show that xanthophylls possess high anti-cancer, anti-diabetic, anti-obesity and anti-oxidant properties. In this review, we highlight the recent findings for five xanthophylls, namely astaxanthin, β-cryptoxanthin, fucoxanthin, neoxanthin and zeaxanthin/lutein, and their relevance to cancer prevention.
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