Login Register Cart 0
Generic placeholder image

Current Nutrition & Food Science

Editor-in-Chief

ISSN (Print): 1573-4013
ISSN (Online): 2212-3881

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Momordica charantia Seed and Aryl Extracts Potentiate Growth Inhibition and Apoptosis by Dual Blocking of PI3K/AKT and MAPK Pathways as a Downstream Target of EGFR Signaling in Breast Cancer Cells

Author(s): Guzide Satir Basaran, Hatice Bekci, Ayse Baldemir, Selen Ilgun and Ahmet Cumaoglu*

Volume 16, Issue 5, 2020

Page: [726 - 733] Pages: 8

DOI: 10.2174/1573401315666190712214922

Price: $65

Abstract

Background and Objective: Herbal extracts and plant compounds are increasingly becoming of interest for their therapeutic potential in various cancer types. Momordica charantia is well known for its anti-diabetic, anti-inflammatory, and anti-cancer properties.

Methods: In the present study, we investigated the antiproliferative and pro-apoptotic effects of Momordica charantia seed and aryl extracts on breast cancer cells and explored the underlying molecular mechanisms.

Results: Our results showed that both extract significantly inhibited the growth of MCF-7 and MDA MB-231 cells in a concentration-dependent manner, and induced apoptosis by upregulation of caspase 9 and caspase 3 mRNA levels. In addition, in different incubation time, both extract evidently inhibited EGF and induced EGFR phosphorylation/activation in both cell lines. Moreover, Momordica charantia aryl and seed extracts inhibited phosphorylation/activation of PI3K/AKT and MAPK (ERK and P38) pathways in both cell lines.

Conclusion: The current study clearly demonstrates that the Momordica charantia aryl and seed extracts have the potential to exert its cytotoxic effect on breast cancer cells by a mechanism involving inhibition of EGFR and EGRF related pathways with the induction of apoptosis. The overall finding demonstrates that this plant, especially seed extract, could be a potential source of new anticancer compounds for possible drug development against cancer.

Keywords: Anticancer compounds, AKT, breast cancer, EGFR, MAPK, Momordica charantia.

« Previous Next »
Graphical Abstract

[1]
Kotecha R, Takami A, Espinoza JL. Dietary phytochemicals and cancer chemoprevention: a review of the clinical evidence. Oncotarget 2016; 7(32): 52517-29.
[http://dx.doi.org/10.18632/oncotarget.9593]
[2]
Moradi-Kalbolandi S, Hosseinzade A, Salehi M, Merikhian P, Farahmand L. Monoclonal antibody-based therapeutics, targeting the epidermal growth factor receptor family: from herceptin to Pan HER. J Pharm Pharmacol 2018; 70(7): 841-54.
[http://dx.doi.org/10.1111/jphp.12911] [PMID: 29574771]
[3]
Pal D, Sharma U, Singh SK, Kakkar N, Prasad R. Over-expression of telomere binding factors (TRF1 & TRF2) in renal cell carcinoma and their inhibition by using SiRNA induce apoptosis, reduce cell proliferation and migration invitro. PLoS One 2015; 10(3) e0115651
[http://dx.doi.org/10.1371/journal.pone.0115651] [PMID: 25730259]
[4]
Xie P, Horio F, Fujii I, Zhao J, Shinohara M, Matsukura M. A novel polysaccharide derived from algae extract inhibits cancer progression via JNK, not via the p38 MAPK signaling pathway. Int J Oncol 2018; 52(5): 1380-90.
[PMID: 29512724]
[5]
Lu H, Guo Y, Gupta G, Tian X. Mitogen-activated protein kinase (mapk): new insights in breast cancer. J Environ Pathol Toxicol Oncol 2019; 38(1): 51-9.
[http://dx.doi.org/10.1615/JEnvironPatholToxicolOncol.2018028386] [PMID: 30806290]
[6]
Dhillon AS, Hagan S, Rath O, Kolch W. MAP kinase signalling pathways in cancer. Oncogene 2007; 26(22): 3279-90.
[http://dx.doi.org/10.1038/sj.onc.1210421] [PMID: 17496922]
[7]
Jiang L, Wang Y, Liu G, et al. C-Phycocyanin exerts anti-cancer effects via the MAPK signaling pathway in MDA-MB-231 cells. Cancer Cell Int 2018; 18: 12.
[http://dx.doi.org/10.1186/s12935-018-0511-5] [PMID: 29416441]
[8]
Rampurwala MM, Rocque GB, Burkard ME. Update on adjuvant chemotherapy for early breast cancer. Breast Cancer (Auckl) 2014; 8: 125-33.
[http://dx.doi.org/10.4137/BCBCR.S9454] [PMID: 25336961]
[9]
Meng Y, Liu S, Li J, Meng Y, Zhao X. Preparation of an antitumor and antivirus agent: chemical modification of α-MMC and MAP30 from Momordica Charantia L. with covalent conjugation of polyethyelene glycol. Int J Nanomedicine 2012; 7: 3133-42.
[PMID: 22802682]
[10]
Wang Q, Wu X, Shi F, Liu Y. Comparison of antidiabetic effects of saponins and polysaccharides from Momordica charantia L. in STZ-induced type 2 diabetic mice. Biomed Pharmacother 2019; 109: 744-50.
[http://dx.doi.org/10.1016/j.biopha.2018.09.098] [PMID: 30551527]
[11]
Fraser SP, Diss JKJ, Chioni AM, et al. Voltage-gated sodium channel expression and potentiation of human breast cancer metastasis. Clin Cancer Res 2005; 11(15): 5381-9.
[http://dx.doi.org/10.1158/1078-0432.CCR-05-0327] [PMID: 16061851]
[12]
Dandekar M, Deshpande K. Breast cancer and use of Alternative medicine: a mini review. Res Rev Pharm Pharma Sci 2016; 5: 115-9.
[13]
Ray RB, Raychoudhuri A, Steele R, Nerurkar P. Bitter melon (Momordica charantia) extract inhibits breast cancer cell proliferation by modulating cell cycle regulatory genes and promotes apoptosis. Cancer Res 2010; 70(5): 1925-31.
[http://dx.doi.org/10.1158/0008-5472.CAN-09-3438] [PMID: 20179194]
[14]
Ramachandra SC, Vishwanath P, Nataraj SM, et al. In vitro anti cancer activity of ethanolic extract of Momordica charantia on cervical and breast cancer cell lines. Int J Health Allied Sci 2015; 4: 210-7.
[http://dx.doi.org/10.4103/2278-344X.167649]
[15]
Li CJ, Tsang SF, Tsai CH, Tsai HY, Chyuan JH, Hsu HY. Momordica charantia extract induces apoptosis in human cancer cells through caspase and mitochondria-dependent pathways. Evid Based Complement Alternat Med 2012; 2012, 261971
[http://dx.doi.org/10.1155/2012/261971] [PMID: 23091557]
[16]
Zhang CZ, Fang EF, Zhang HT, Liu LL, Yun JP. Momordica charantia lectin exhibits antitumor activity towards hepatocellular carcinoma. Invest New Drugs 2015; 33(1): 1-11.
[http://dx.doi.org/10.1007/s10637-014-0156-8] [PMID: 25200916]
[17]
Yim K, Park HS, Kim DM, Lee YS, Lee A. Image analysis of her2 immunohistochemical staining of surgical breast cancer specimens. Yonsei Med J 2019; 60(2): 158-62.
[http://dx.doi.org/10.3349/ymj.2019.60.2.158] [PMID: 30666837]
[18]
Wee P, Wang Z. Epidermal growth factor receptor cell proliferation signaling pathways. Cancers (Basel) 2017; 9(5): 9.
[PMID: 28513565]
[19]
Zhang Y, Zheng L, Zhang J, et al. Antitumor activity of taspine by modulating the EGFR signaling pathway of Erk1/2 and Akt in vitro and in vivo. Planta Med 2011; 77(16): 1774-81.
[http://dx.doi.org/10.1055/s-0030-1271132] [PMID: 21614750]
[20]
Jiang W, Tian W, Ijaz M, Wang F. Inhibition of EGF-induced migration and invasion by sulfated polysaccharide of Sepiella maindroni ink via the suppression of EGFR/Akt/p38 MAPK/MMP-2 signaling pathway in KB cells. Biomed Pharmacother 2017; 95: 95-102.
[http://dx.doi.org/10.1016/j.biopha.2017.08.050] [PMID: 28830011]
[21]
Huang WC, Tsai TH, Huang CJ, et al. Inhibitory effects of wild bitter melon leaf extract on Propionibacterium acnes-induced skin inflammation in mice and cytokine production in vitro. Food Funct 2015; 6(8): 2550-60.
[http://dx.doi.org/10.1039/C5FO00550G] [PMID: 26098998]
[22]
Kim K, Kim HY. Bitter melon (Momordica charantia) extract suppresses cytokine induced activation of MAPK and NF-κB in pancreatic β-Cells. Food Sci Biotechnol 2011; 20(2): 531-5.
[http://dx.doi.org/10.1007/s10068-011-0074-x]
[23]
Weng JR, Bai LY, Chiu CF, Hu JL, Chiu SJ, Wu CY. Cucurbitane triterpenoid from Momordica charantia induces apoptosis and autophagy in breast cancer cells, in part, through peroxisome proliferator-activated receptor γ activation. Evid Based Complement Alternat Med 2013; 2013, 935675
[http://dx.doi.org/10.1155/2013/935675] [PMID: 23843889]
[24]
Richmond RA, Vuong QV, Scarlet CJ. Cytotoxic effect of bitter melon (Momordica charantia L.) ethanol extract and its fractions on pancreatic cancer cells in vitro. ERHM 2017; 2(4): 139-49.
[http://dx.doi.org/10.14218/ERHM.2017.00032]
[25]
Gu HZ, Lin RR, Wang HC, Zhu XJ, Hu Y, Zheng FY. Effect of Momordica charantia protein on proliferation, apoptosis and the AKT signal transduction pathway in the human endometrial carcinoma Ishikawa H cell line in vitro. Oncol Lett 2017; 13(5): 3032-8.
[http://dx.doi.org/10.3892/ol.2017.5830] [PMID: 28521410]
[26]
Manoharan G, Jaiswal SR, Singh J. Effect of α, β momorcharin on viability, caspase activity, cytochrome c release and on cytosolic calcium levels in different cancer cell lines. Mol Cell Biochem 2014; 388(1-2): 233-40.
[http://dx.doi.org/10.1007/s11010-013-1914-1] [PMID: 24297707]

Rights & Permissions Print Cite
Article Metrics
12
© 2024 Bentham Science Publishers | Privacy Policy