A REVIEW ON BIOACTIVE PHYTOCHEMICALS AND IT’S MECHANISM ON CANCER TREATMENT AND PREVENTION BY TARGETING MULTIPLE CELLULAR SIGNALING PATHWAYS
DOI:
https://doi.org/10.22159/ijpps.2021v13i12.42798Keywords:
Cancer, Medicinal plants, Phytochemicals, Signaling pathwaysAbstract
In developing and developed countries, cancer is a significant health problem in people. Cancer becomes the second greatest cause of death in human after cardiovascular disease. However, significant advancements in modern cancer therapies have a beneficial impact on survival, chemotherapy and radiation therapy. Plants fulfill our basic needs to continue life and provide natural products that help to cure disease. The medicinal plants are readily available and have no toxicity as compared to modern drugs. Phytochemicals act on metabolic pathways and inhibit tumor growth, the development of cancerous cells, and replication by different mechanisms. Apigenin's chemo-preventive and anticancer activities have been demonstrating in numerous studies. Curcumin is a polyphenolic compound isolated from the Curcuma longa plant. EGCG, a polyphenol in black, white, and green tea is a chemo-preventive effect against many cancers by targeting multiple pathways. Normal cell growth and cell proliferation are closely regulated processes. The JAK-STAT (Janus kinase-signal transducer and activator of transcription) pathway controls gene expression during different processes, including proliferation, initiation, and apoptosis. The transcription factors are associated with the growth of cancer cells and control a cellular function in the disease. Mitogen-activated protein kinase (MAPK) is a class of serine and threonine kinase that includes ERK (extracellular regulated kinase), JNK (c-Jun N-terminal kinases), and p38. This review paper describes natural phytochemical compounds, their molecular targets and mechanisms of action.
Downloads
References
Sudha M. Anti cancer herbs used in Siddha system of medicine: a review. IJPPR. 2018;12:118-34.
Chanchal Dilip Kumar. Various medicinal plants used in the treatment of anticancer activity. Int J Pharm Sci. 2017;9:1424-9.
Sharma Deepika, Dangi DCBS. Role of plants in treating cancer: a review. Int J Adv Res. 2016;4(7):901-7. doi: 10.21474/IJAR01/969.
Adhikari Partha Pradip, Paul Satya Bhusan. Medicinally important plant cleome gynandra: A phytochemical and pharmacological explanation. Asian J Pharm Clin Res. 2018;11(1):21-6. doi: 10.22159/ajpcr.2017.v11i1.22037.
Cragg Gordon M, Newman David J. Plants as a source of anti-cancer agents. J Ethnopharmacol. 2005;100(1-2):72-9. doi: 10.1016/j.jep.2005.05.011, PMID 16009521.
Balabhaskar R, Rajendra Kumar A, Selvarajan S, Faridha A, Gayathri Gunalan. Potential natural products with anticancer properties and their applications. Asian J Pharm Clin Res. 2019;12:27-33. doi: 10.22159/ajpcr.2019.v12i5.32817.
Wang Yuan-Chuen, Huang Kai-Ming. In vitro anti-inflammatory effect of apigenin in the Helicobacter pylori-infected gastric adenocarcinoma cells. Food Chem Toxicol. 2013;53:376-83. doi: 10.1016/j.fct.2012.12.018, PMID 23266501.
Bruno Andreina, Siena Liboria, Gerbino Stefania, Ferraro Maria, Chanez Pascal, Giammanco Marco, Gjomarkaj Mark, Pace Elisabetta. Apigenin affects leptin/leptin receptor pathway and induces cell apoptosis in lung adenocarcinoma cell line. Eur J Cancer. 2011;47(13):2042-51. doi: 10.1016/j.ejca.2011.03.034, PMID 21550230.
Liu Xuan, Ji Qing, Ye Naijing, Sui Hua, Zhou Lihong, Zhu Huirong, Fan Zhongze, Cai Jianfeng, Li Q. Berberine inhibits invasion and metastasis of colorectal cancer cells via COX-2/PGE 2 mediated JAK2/STAT3 signaling pathway. PLOS ONE. 2015;10(5):e0123478. doi: 10.1371/journal.pone.0123478, PMID 25954974.
Tai WP, Luo HS. The inhibit effect of berberine on human colon cell line cyclooxygenase-2. Zhonghua Nei Ke Za Zhi. 2003;42(8):558-60. PMID 14505547.
Kim Hak Su, Kim Myung Jin, Kim Eun Ju, Yang Young, Lee Myeong-Sok, Lim Jong-Seok. Berberine-induced AMPK activation inhibits the metastatic potential of melanoma cells via reduction of ERK activity and COX-2 protein expression. Biochem Pharmacol. 2012;83(3):385-94. doi: 10.1016/j.bcp.2011.11.008, PMID 22120676.
Krisnamurti Desak Gede Budi, Wanandi Septelia Inawati, Louisa Melva. Curcumin increases the sensitivity of breast cancer cells to tamoxifen by inhibiting MRP2 mrna expression of efflux transporter MRP2. Int J Appl Pharm. 2019;11:88-90. doi: 10.22159/ijap.2019.v11s6.33553.
Yu Siwang, Shen Guoxiang, Khor Tin Oo, Kim Jung Hwan, Kong Ah-Ng Tony. Curcumin inhibits Akt/mammalian target of rapamycin signaling through protein phosphatase-dependent mechanism. Mol Cancer Ther. 2008;7(9):2609-20. doi: 10.1158/1535-7163.MCT-07-2400, PMID 18790744.
Harper Curt E, Patel Brijesh B, Wang Jun, Eltoum Isam A, Lamartiniere Coral A. Epigallocatechin‐3‐gallate suppresses early stage, but not late-stage prostate cancer in TRAMP mice: mechanisms of action. Prostate. 2007;67(14):1576-89. doi: 10.1002/pros.20643, PMID 17705241.
Singh Tripti, Katiyar Santosh K. Green tea polyphenol,(–)-epigallocatechin-3-gallate, induces toxicity in human skin cancer cells by targeting β-catenin signaling. Toxicol Appl Pharmacol. 2013;273(2):418-24. doi: 10.1016/j.taap.2013.09.021, PMID 24096034.
Lim Do Y, Park Jung Han Yoon. Induction of p53 contributes to the apoptosis of HCT-116 human colon cancer cells induced by the dietary compound fisetin. Am J Physiol Gastrointest Liver Physiol. 2009;296(5):G1060-8. doi: 10.1152/ajpgi.90490.2008, PMID 19264955.
Liao Yi-Chen, Shih Yuan-Wei, Chao Chang-Hung, Lee Xin-Yan, Chiang Tai-An. Involvement of the ERK signaling pathway in fisetin reduces invasion and migration in the human lung cancer cell line A549. J Agric Food Chem. 2009;57(19):8933-41. doi: 10.1021/jf902630w, PMID 19725538.
Lopez Lazaro Miguel, Willmore Elaine, Austin Caroline A. Cells lacking DNA topoisomerase IIβ are resistant to genistein. J Nat Prod. 2007;70(5):763-7. doi: 10.1021/np060609z, PMID 17411092.
Magee Pamela J, Rowland Ian R. Phyto-oestrogens, their mechanism of action: current evidence for a role in breast and prostate cancer. Br J Nutr. 2004;91(4):513-31. doi: 10.1079/BJN20031075, PMID 15035679.
Gacche Rajesh N, Shegokar Harshala D, Gond Dhananjay S, Yang Zhenzhou, Jadhav Archana D. Evaluation of selected flavonoids as antiangiogenic, anticancer, and radical scavenging agents: an experimental and in silico analysis. Cell Biochem Biophys. 2011;61(3):651-63. doi: 10.1007/s12013-011-9251-z, PMID 21830125.
Yi Xiaofang, Zuo Jiangcheng, Tan Chao, Xian Sheng, Luo Chunhua, Chen Sai, Yu Liangfang, Luo Yucheng. Kaempferol, a flavonoid compound from Gynura medica induced apoptosis and growth inhibition in mcf-7 breast cancer cell. Afr J Tradit Complement Altern Med. 2016;13(4):210-5. doi: 10.21010/ajtcam.v13i4.27, PMID 28852738.
To Kenneth KW, Yu L, Liu Shuwen, Fu Jianhua, Cho Chi Hin. Constitutive AhR activation leads to concomitant ABCG2‐mediated multidrug resistance in cisplatin‐resistant esophageal carcinoma cells. Mol Carcinog. 2012;51(6):449-64. doi: 10.1002/mc.20810, PMID 21678497.
Giovannucci Edward, Ascherio A, Rimm EB, Stampfer MJ, Colditz GA, Willett WC. Intake of carotenoids and retino in relation to risk of prostate cancer. J Natl Cancer Inst. 1995;87(23):1767-76. doi: 10.1093/jnci/87.23.1767, PMID 7473833.
Wang Hongxian, Tao Linyu, Qi K, Zhang Haoyun, Feng Duo, Wei Wenjun, Kong Heng, Chen Tianwen, Lin Qiusheng. Quercetin reverses tamoxifen resistance in breast cancer cells. J BUON. 2015;20(3):707-13. PMID 26214621.
Al-Fayez Mohammad, Cai Hong, Tunstall Richard, Steward William P, Gescher Andreas J. Differential modulation of cyclooxygenase-mediated prostaglandin production by the putative cancer chemopreventive flavonoids tricin, apigenin and quercetin. Cancer Chemother Pharmacol. 2006;58(6):816-25. doi: 10.1007/s00280-006-0228-3, PMID 16552572.
Bishayee Anupam. Cancer prevention and treatment with resveratrol: from rodent studies to clinical trials. Cancer Prev Res (Phila). 2009;2(5):409-18. doi: 10.1158/1940-6207.CAPR-08-0160, PMID 19401532.
Zykova Tatyana A, Zhu Feng, Zhai Xiuhong, Ma Wei‐Ya, Ermakova Svetlana P, Lee Ki Won, Bode Ann M, Dong Zigang. Resveratrol directly targets COX‐2 to inhibit carcinogenesis. Molecular carcinogenesis: published in cooperation with the University of Texas M D Anderson Cancer Center. 2008;10:797-805.
Park, Sin Aye, Hye Kyung Na, Young Joon Surh. Resveratrol suppresses 4-hydroxyestradiol-induced transformation of human breast epithelial cells by blocking IκB kinaseβ-NF-κB signalling. Free Radical Res. 2012;8:1051-7.
Shanmugam Muthu K, Dai Xiaoyun, Kumar Alan Prem, Tan Benny KH, Sethi Gautam, Bishayee Anupam. Ursolic acid in cancer prevention and treatment: molecular targets, pharmacokinetics and clinical studies. Biochem Pharmacol. 2013;85(11):1579-87. doi: 10.1016/j.bcp.2013.03.006, PMID 23499879.
Iqbal Javed, Abbasi Banzeer Ahsan, Ahmad Riaz, Mahmood Tariq, Kanwal Sobia, Ali Barkat, Khalil Ali Talha, Shah Sayed Afzal, Alam Muhammad Maqsood, Badshah Hussain. Ursolic acid a promising candidate in the therapeutics of breast cancer: current status and future implications. Biomed Pharmacother. 2018;108:752-6. doi: 10.1016/ j.biopha.2018.09.096, PMID 30248543.
Zhang Yi-Ying, Deng Tao, Hu Zhi-Fang, Zhang Qiu-Ping, Zhang Jing, Jiang Hua. Mechanisms of inhibiting proliferation and inducing apoptosis of human gastric cancer cell line SGC7901 by ursolic acid. Ai Zheng. 2006;25(4):432-7. PMID 16613675.
D’Agostini Francesco, Izzotti Alberto, Balansky Roumen M, Bennicelli Carlo, De Flora Silvio. Modulation of apoptosis by cancer chemopreventive agents. Mutat Res. 2005;591(1-2):173-86. doi: 10.1016/j.mrfmmm.2005.03.034, PMID 16137721.
Li-Weber Min. Targeting apoptosis pathways in cancer by Chinese medicine. Cancer Lett. 2013;332(2):304-12. doi: 10.1016/j.canlet.2010.07.015, PMID 20685036.
Khan Naghma, Mukhtar Hasan. Multitargeted therapy of cancer by green tea polyphenols. Cancer Lett. 2008;269(2):269-80. doi: 10.1016/j.canlet.2008.04.014, PMID 18501505.
Murakami Akira, Ashida Hitoshi, Terao Junji. Multitargeted cancer prevention by quercetin. Cancer Lett. 2008;269(2):315-25. doi: 10.1016/j.canlet.2008.03.046, PMID 18467024.
Manu KA, Kuttan Girija. Ursolic acid induces apoptosis by activating p53 and caspase-3 gene expressions and suppressing NF-kappaB mediated activation of bcl-2 in B16F-10 melanoma cells. Int Immunopharmacol. 2008;8(7):974-81. doi: 10.1016/j.intimp.2008.02.013, PMID 18486908.
Rezaei Parisa Fathi, Fouladdel Shamileh, Ghaffari Seyed Mahmood, Amin Gholamreza, Azizi Ebrahim. Induction of G1 cell cycle arrest and cyclin D1 down-regulation in response to pericarp extract of Baneh in human breast cancer T47D cells. Daru. 2012;20(1):101. doi: 10.1186/2008-2231-20-101, PMID 23351343.
Araujo Joao R, Gonçalves Pedro, Martel Fatima. Chemopreventive effect of dietary polyphenols in colorectal cancer cell lines. Nutr Res. 2011;31(2):77-87. doi: 10.1016/j.nutres.2011.01.006, PMID 21419311.
Cui Jing, Sun Renhu, Yu Yangping, Gou Shanmiao, Zhao Gang, Wang Chunyou. Antiproliferative effect of resveratrol in pancreatic cancer cells. Phytother Res. 2010;24(11):1637-44. doi: 10.1002/ptr.3157, PMID 21031621.
Cai, Jing, Zhao Xiang-Li, Liu An-Wen, Nian Hua, Zhang Shu-Hui. Apigenin inhibits hepatoma cell growth through alteration of gene expression patterns. Phytomedicine. 2011;18(5):366-73. doi: 10.1016/j.phymed.2010.08.006, PMID 20850954.
Yu, Hua, Richard Jove Richard. The STATs of cancer- new molecular targets come of age. Nature Reviews Cancer. 2004;4(2):97-105. doi: 10.1038/nrc1275, PMID 14964307.
Garcia Roy, Bowman TL, Niu G, Yu H, Minton S, Muro-Cacho CA, Cox CE, Falcone R, Fairclough R, Parsons S, Laudano A, Gazit A, Levitzki A, Kraker A, Jove R. Constitutive activation of Stat3 by the Src and JAK tyrosine kinases participates in growth regulation of human breast carcinoma cells. Oncogene. 2001;20(20):2499-513. doi: 10.1038/sj.onc.1204349, PMID 11420660.
Masuda, Muneyuki, Suzui Masumi, Lim Jin TE, Weinstein I Bernard. Epigallocatechin-3-gallate inhibits activation of HER-2/neu and downstream signaling pathways in human head and neck and breast carcinoma cells. Clinical Cancer Research. 2003;9(9):3486-91. PMID 12960141.
Muthian, Gladson, John J. Bright John J. Quercetin, a flavonoid phytoestrogen, ameliorates experimental allergic encephalomyelitis by blocking IL-12 signaling through JAK-STAT pathway in T lymphocyte. J Clinical Immunology. 2004;24(5):542-52. doi: 10.1023/B:JOCI.0000040925.55682.a5, PMID 15359113.
Pratheeshkumar Poyil, Sreekala Chakkenchath, Zhang Zhuo, Budhraja Amit, Ding Songze, Son Young-Ok, Wang Xin. Cancer prevention with promising natural products: mechanisms of action and molecular targets. Anti-Cancer Agents in Medicinal Chemistry (formerly current medicinal chemistry-anti-cancer agents). 2012;10:1159-84.
Garnett, Mathew J, Richard Marais Richard. Guilty as charged: B-RAF is a human oncogene. Cancer Cell. 2004;6(4);313-9. doi: 10.1016/j.ccr.2004.09.022, PMID 15488754.
Hua Wen Feng, Fu Yong Shui, Liao Yi-Ji, Xia Wen-Jie, Chen Yang Chao, Zeng Yi-Xin, Kung Hsiang-Fu, Xie Dan. Curcumin induces down-regulation of EZH2 expression through the MAPK pathway in MDA-MB-435 human breast cancer cells. Eur J Pharmacol. 2010;637(1-3):16-21. doi: 10.1016/j.ejphar.2010.03.051. PMID 20385124.
Wu, Chia Chieh, Cheng Chun Hsiang, Lee Yi-Hui, Chang Ing-Lin, Chen Hsin-Yao, Hsieh Chen-Pu, Chueh Pin-Ju. Ursolic acid triggers apoptosis in human osteosarcoma cells via caspase activation and the ERK1/2 MAPK pathway. Journal of Agricultural and Food Chemistry. 2016;64(21):4220-6. doi: 10.1021/acs.jafc.6b00542, PMID 27171502.
Chaturvedi MM, Sung B, Yadav VR, Kannappan R, Aggarwal BB. NF-κB addiction and its role in cancer: ‘one size does not fit all’. Oncogene. 2011;30(14):1615-30. doi: 10.1038/onc.2010.566, PMID 21170083.
Pahl HL. Activators and target genes of Rel/NF-kappaB transcription factors. Oncogene. 1999;18(49):6853-66. doi: 10.1038/sj.onc.1203239. PMID 10602461.
Coope HJ, Atkinson PG, Huhse B, Belich M, Janzen J, Holman MJ, Klaus GG, Johnston LH, Ley SC. CD40 regulates the processing of NF-kappaB2 p100 to p52. EMBO J. 2002;21(20):5375-85. doi: 10.1093/emboj/cdf542, PMID 12374738.
Manna, Sunil K, Asok Mukhopadhyay Asok, Bharat B, Aggarwal Bharat B. Resveratrol suppresses TNF-induced activation of nuclear transcription factors NF-κB, activator protein-1, and apoptosis: potential role of reactive oxygen intermediates and lipid peroxidation. Journal of Immunology. 2000;164(12):6509-19. doi: 10.4049/jimmunol.164.12.6509, PMID 10843709.
Divya Chandrasekhar S, Radhakrishna Pillai M. Antitumor action of curcumin in human papillomavirus-associated cells involves downregulation of viral oncogenes, prevention of NFκB and AP-1 translocation, and modulation of apoptosis. Molecular carcinogenesis: published in cooperation with the University of Texas M D Anderson Cancer Center. 2006;45:320-32.
Published
How to Cite
Issue
Section
Copyright (c) 2021 VARSHA L. BHUTADIYA, KINNARI N. MISTRY
This work is licensed under a Creative Commons Attribution 4.0 International License.