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  • ISSN[Online] : 2643-9875  ||  ISSN[Print] : 2643-9840

Volume 06 Issue 09 September 2023

The Effect of Bitter Melon Extract (Momordica Charantia) On CASPASE-9 and Bcl-2 Proteins Expression
1Desti Rahmasari, 2Titiek Sumarawati, 3Setyo Trisnadi
1Postgraduate student of Biomedical Sciences, Faculty of Medicine, Universitas Islam Sultan Agung, Jl Kaligawe KM 4 Semarang 50012
2,3Department of Biomedical Sciences, Faculty of Medicine, Universitas Islam Sultan Agung, Jl Kaligawe KM 4 Semarang 50012
DOI : https://doi.org/10.47191/ijmra/v6-i9-40

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ABSTRACT:

Breast cancer has a significant morbidity and death rate worldwide, thus various therapeutic strategies, including the phytopharmaca approach, must be researched further. Bitter melon (Momordica charantia) extract is predicted to have anticancer properties due to its influence on Caspase-9 and BcL2 proteins, which will be shown in this in vitro investigation utilizing MCF-7 cell culture. This study was an in vitro laboratory experimental study with a post-test-only control group design. The doses of Momordica charantia extract used were 125 μg/ml, 500 μg/ml, and 1,000 μg/ml. Caspase-9 and BcL2 protein expression in MCF-7cell culture was measured by immunocytochemistry method, Shapiro Wilk, Levene Test, One Way Anova, and Post Hoc LSD. Administration of Momordica charantia extract at a dose of 500 μg/ml and 1,000 μg/ml significantly increased the average expression of Caspase-9 protein (p = 0.044 and p = 0.004 respectively), but not at a dose of 125 μg/mL (p = 0.125). Administration of bitter melon extract at doses of 125 μg/ml, 500 μg/ml, and 1,000 μg/ml significantly reduced the average BcL2 protein expression (p < 0.001, p < 0.001, and p = 0.001 respectively). Momordica charantia extract has the potential to be employed as an anti-breast cancer agent due to its ability to increase the average expression of Caspase-9 protein while reducing the average expression of BcL2 protein.

KEYWORDS:

Breast cancer, CASPASE-9, BcL-2, bitter melon

REFERENCES
1) Labrèche F, Goldberg MS, Hashim D, Weiderpass E. Breast cancer. In: Occupational Cancers. 2020.

2) World Health Organization. Indonesia Fact Sheet Cancer Data GLOBOCAN. 2020.

3) Ibrahim A, Sandhika W, Budipramana VS. Uji Efektifitas Ekstrak Etanol Daun Annona Muricata Terhadap Sel Kanker Payudara MCF-7. Jurnal Manajemen Kesehatan Yayasan RSDr Soetomo. 2020;6(1).

4) Dandawate PR, Subramaniam D, Padhye SB, Anant S. Bitter melon: a panacea for inflammation and cancer. Chinese journal of natural medicines. 2016 Feb;14(2):81–100.

5) Jia S, Shen M, Zhang F, Xie J. Recent Advances in Momordica charantia: Functional Components and Biological Activities. International journal of molecular sciences. 2017 Nov 28;18(12):2555.

6) Vishwanath P, Shobha CR, Suma MN, Prashant A, Rangaswamy C, Gowdappa B. In vitro anti-cancer activity of ethanolic extract of Momordica charantia on cervical and breast cancer cell lines. International Journal of Health & Allied Sciences. 2015;4(4):210.

7) Sebaugh JL. Guidelines for accurate EC50/IC50 estimation. Pharmaceutical Statistics. 2011;10(2):128–34.

8) Ansari Aa, Singh J, Aminuddin M. Biochemical characterization of Momordica charantia (leaf and fruit) and effect of soluble extract on MCF-7breast cancer cell lines. Cell Biology and Development. 2019;3(1).

9) Earnshaw WC, Martins LM, Kaufmann SH. Mammalian Caspases: Structure, Activation, Substrates, and Functions During Apoptosis. Annual Review of Biochemistry. 1999;68(1):383–424.

10) Qiao M, Yang J, Zhao Y, Zhu Y, Wang X, Wang X, et al. Antiliver Fibrosis Screening of Active Ingredients from Apium graveolens L. Seeds via GC-TOF-MS and UHPLC-MS/MS. Evidence-based Complementary and Alternative Medicine. 2020;

11) Oeffinger KC, Fontham ETH, Etzioni R, Herzig A, Michaelson JS, Shih YCT, et al. Breast Cancer Screening for Women at Average Risk: 2015 Guideline Update From the American Cancer Society. JAMA. 2015 Oct 20;314(15):1599–614.

12) Agu Yosali M, Bintari N. The Relationship Of Menarche Age With Breast Cancer Events In Women Age 25-50 Years In The Short Center Of Indonesia Breast Cancer Foundation (Ykpi) Jakarta. Jurnal Ilmiah Wijaya. 2020;11(2).

13) Fortner RT, Sisti J, Chai B, Collins LC, Rosner B, Hankinson SE, et al. Parity, breastfeeding, and breast cancer risk by hormone receptor status and molecular phenotype: Results from the Nurses’ Health Studies. Breast Cancer Research. 2019;21(1).

14) Evans DG, Harkness EF, Howel S, Woodward ER, Howell A, Lalloo F. Young age at first pregnancy does protect against early onset breast cancer in BRCA1 and BRCA2 mutation carriers. Breast Cancer Research and Treatment. 2018;167(3).

15) Chien TJ, Hsu CH, Liu CY, Fang CJ. Effect of acupuncture on hot flush and menopause symptoms in breast cancer - A systematic review and meta-analysis. PLoS ONE. 2017;12(8).

16) Kolb R, Zhang W. Obesity and Breast Cancer: A Case of Inflamed Adipose Tissue. Cancers. 2020 Jun 1;12(6):1–18.

17) Lofterød T, Frydenberg H, Flote V, Eggen AE, McTiernan A, Mortensen ES, et al. Exploring the effects of lifestyle on breast cancer risk, age at diagnosis, and survival: the EBBA-Life study. Breast Cancer Research and Treatment. 2020 Jul 1;182(1):215.

18) Zhong LY, Xiang X, Ye J, Lu W, Lv J, Zhang DW, et al. Application of the MCF-7Breast Cancer Cells in Endocrine-Disrupting Area. Advanced Materials Research. 2014;955–959:928–35.

19) Lee A V., Oesterreich S, Davidson NE. MCF-7Cells - Changing the Course of Breast Cancer Research and Care for 45 Years. Vol. 107, Journal of the National Cancer Institute. 2015.

20) Geltmeier A, Rinner B, Bade D, Meditz K, Witt R, Bicker U, et al. Characterization of Dynamic Behaviour of MCF7 and MCF10A Cells in Ultrasonic Field Using Modal and Harmonic Analyses. PloS one. 2015 Aug 4;10(8):e0134999–e0134999.

21) Booms A, Coetzee GA, Pierce SE. MCF-7as a Model for Functional Analysis of Breast Cancer Risk Variants. Cancer epidemiology, biomarkers & prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2019/07/10. 2019 Oct;28(10):1735–45.

22) Reed JC. Mechanisms of apoptosis. The American journal of pathology. 2000 Nov;157(5):1415–30.

23) Xu X, Lai Y, Hua ZC. Apoptosis and apoptotic body: disease message and therapeutic target potentials. Bioscience reports. 2019 Jan 18;39(1):BSR20180992.

24) Julien O, Zhuang M, Wiita AP, O’Donoghue AJ, Knudsen GM, Craik CS, et al. Quantitative MS-based enzymology of caspases reveals distinct protein substrate specificities, hierarchies, and cellular roles. Proceedings of the National Academy of Sciences of the United States of America. 2016/03/22. 2016 Apr 5;113(14):E2001–10.

25) Li P, Zhou L, Zhao T, Liu X, Zhang P, Liu Y, et al. Caspase-9: structure, mechanisms and clinical application. Oncotarget. 2017 Apr 4;8(14):23996–4008.

26) Shang J, Yang F, Wang Y, Wang Y, Xue G, Mei Q, et al. MicroRNA-23a Antisense Enhances 5-Fluorouracil Chemosensitivity Through APAF-1/Caspase-9 Apoptotic Pathway in Colorectal Cancer Cells. Journal of Cellular Biochemistry. 2014;115(4):772–84.

27) Hu Q, Wu D, Chen W, Yan Z, Yan C, He T, et al. Molecular determinants of Caspase-9 activation by the Apaf-1 apoptosome. Proceedings of the National Academy of Sciences of the United States of America. 2014/10/13. 2014 Nov 18;111(46):16254–61.

28) Braun F, de Carné Trécesson S, Bertin-Ciftci J, Juin P. Protect and serve: BcL2 proteins as guardians and rulers of cancer cell survival. Cell cycle (Georgetown, Tex). 2013/08/13. 2013 Sep 15;12(18):2937–47.

29) Um HD. BcL2 family proteins as regulators of cancer cell invasion and metastasis: a review focusing on mitochondrial respiration and reactive oxygen species. Oncotarget. 2016 Feb 2;7(5):5193–203.

30) Qian S, Wei Z, Yang W, Huang J, Yang Y, Wang J. The role of BCL2 family proteins in regulating apoptosis and cancer therapy. Frontiers in oncology. 2022 Oct 12;12:985363.

31) Morris JL, Gillet G, Prudent J, Popgeorgiev N. BcL2 Family of Proteins in the Control of Mitochondrial Calcium Signalling: An Old Chap with New Roles. International journal of molecular sciences. 2021 Apr 2;22(7):3730.

32) Hafezi S, Rahmani M. Targeting BCL2 in Cancer: Advances, Challenges, and Perspectives. Cancers. 2021 Mar 14;13(6):1292.

33) Kapoor I, Bodo J, Hill BT, Hsi ED, Almasan A. Targeting BCL2 in B-cell malignancies and overcoming therapeutic resistance. Cell death & disease. 2020 Nov 2;11(11):941.

34) Hatok J, Racay P. BcL2 family proteins: master regulators of cell survival. Biomolecular Concepts. 2016;7(4):259–70.

35) Flores-Romero H, Hohorst L, John M, Albert MC, King LE, Beckmann L, et al. BCL2-family protein tBID can act as a BAX-like effector of apoptosis. The EMBO journal. 2021/12/21. 2022 Dec 17;41(2):e108690–e108690.

36) Bleicken S, Hantusch A, Das KK, Frickey T, Garcia-Saez AJ. Quantitative interactome of a membrane BcL2 network identifies a hierarchy of complexes for apoptosis regulation. Nature communications. 2017 Jul 13;8(1):73.

37) Gibson CJ, Davids MS. BCL2 Antagonism to Target the Intrinsic Mitochondrial Pathway of Apoptosis. Clinical cancer research: an official journal of the American Association for Cancer Research. 2015 Nov 15;21(22):5021–9.

38) Aniogo EC, George BPA, Abrahamse H. Role of BcL2 Family Proteins in Photodynamic Therapy Mediated Cell Survival and Regulation. Molecules (Basel, Switzerland). 2020 Nov 13;25(22):5308.

39) Villarreal-La Torre VE, Guarniz WS, Silva-Correa C, Cruzado-Razco L, Siche R. Antimicrobial activity and chemical composition of Momordica Charantia: A review. Vol. 12, Pharmacognosy Journal. 2020.

40) Alshehri MA. Anticancer activity of methanolic extarct of Momordica charantia against human colon, liver and breast cancer cell lines-In vitro. Journal of Biology. 2016;6(6).

41) Sur S, Ray RB. Bitter Melon (Momordica Charantia), a Nutraceutical Approach for Cancer Prevention and Therapy. Cancers. 2020 Jul 27;12(8):2064.

42) Fang EF, Froetscher L, Scheibye-Knudsen M, Bohr VA, Wong JH, Ng TB. Emerging Antitumor Activities of the Bitter Melon (Momordica charantia). Current protein & peptide science. 2019;20(3):296–301.

43) 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 Research. 2010;70(5):1925–31.

44) Liaw CC, Huang HC, Hsiao PC, Zhang LJ, Lin ZH, Hwang SY, et al. 5β,19-Epoxycucurbitane Triterpenoids from Momordica charantia and Their Anti-Inflammatory and Cytotoxic Activity. Planta Medica. 2014;81(01):62–70.

45) Raina K, Kumar D, Agarwal R. Promise of bitter melon (Momordica charantia) bioactives in cancer prevention and therapy. Seminars in cancer biology. 2016/07/21. 2016 Oct;40–41:116–29.

46) Spronk I, Schellevis FG, Burgers JS, de Bock GH, Korevaar JC. Incidence of isolated local breast cancer recurrence and contralateral breast cancer: A systematic review. Breast. 2018;39:70–9.

47) Lim B, Greer Y, Lipkowitz S, Takebe N. Novel apoptosis-inducing agents for the treatment of cancer, a new arsenal in the toolbox. Cancers (Basel). 2019;11(8):1–40.

48) Lukyanova NY, Rusetskya N v., Tregubova NA, Chekhun VF. Molecular profile and cell cycle in MCF-7cells resistant to cisplatin and doxorubicin. Exp Oncol. 2009;31(2):87–91.

49) Ju JH, Jeon MJ, Yang W, Lee KM, Seo HS, Shin I. Induction of apoptotic cell death by Pharbitis nil extract in HER2-overexpressing MCF-7cells. J Ethnopharmacol [Internet]. 2011;133(1):126–31. Available from: http://dx.doi.org/10.1016/j.jep.2010.09.021

50) Jin S, Zhang QY, Kang XM, Wang JX, Zhao WH. Daidzein induces MCF-7breast cancer cell apoptosis via the mitochondrial pathway. Annals of Oncology [Internet]. 2010;21(2):263–8. Available from: https://doi.org/10.1093/annonc/mdp499

51) Comşa Ş, Cîmpean AM, Raica M. The story of MCF-7breast cancer cell line: 40 Years of experience in research. Anticancer Res. 2015;35(6):3147–54.

52) 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 Mar 1;70(5):1925–31.

53) 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. Evidence-based Complementary and Alternative Medicine. 2012;2012.

54) Chen G, Zhou D, Li XZ, Jiang Z, Tan C, Wei XY, et al. A natural chalcone induces apoptosis in lung cancer cells: 3D-QSAR, docking and an in vivo/vitro assay. Sci Rep. 2017 Dec 1;7(1).

55) Ramos S. Effects of dietary flavonoids on apoptotic pathways related to cancer chemoprevention. Vol. 18, Journal of Nutritional Biochemistry. 2007. p. 427–42.

56) Koosha S, Alshawsh MA, Yeng LC, Seyedan A, Mohamed Z. An association map on the effect of flavonoids on the signaling pathways in colorectal cancer. Vol. 13, International Journal of Medical Sciences. Ivyspring International Publisher; 2016. p. 374–85.

57) Veeramuthu D, Raja WRT, Al-Dhabi NA, Savarimuthu I. Flavonoids: Anticancer Properties. Flavonoids - From Biosynthesis to Human Health. 2017;

58) Panche AN, Diwan AD, Chandra SR. Flavonoids: An overview. J Nutr Sci. 2016;5.
Volume 06 Issue 09 September 2023

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