Investigating the Effects of the Ethyl Acetate Fraction of Mas Banana Bracts: Suppressing Cell Growth, Promoting Cell Death, and Targeting Specific Molecules in Hela Cells
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Abstract
The leading cause of cancer-related deaths among women worldwide is cervical cancer, a prevalent malignant illness that mostly affects women. The development of plant-based natural medications has received particular attention in the field of complementary therapies in recent years. Phytochemicals obtained from plants are intriguing candidates for cancer treatment and prevention because they can impede the processes that cause cancer growth. The purpose of this investigation was to determine the anticancer activity of ethyl acetate fraction of mas banana bract (EAMB) against HeLa cervical cancer cells. The antproliferative, and apoptotic effects of EAMB was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and Flow cytometry, respectively. The levels of Epidermal Growth Factor Receptor (EGFR), retinoblastoma protein (pRb), Ki-67, and Caspase-3 were measured by enzyme linked immunosorbent assay (ELISA). The MTT assay showed that EAMB significantly reduced HeLa cell viability, with a 59.12% decrease at 887.7 µl/mL EAMB combined with 41.6 µl/mL cisplatin after 72 hours of incubation. Flow cytometry revealed that EAMB increased late apoptosis up to 34.47% at 1775.4 µl/mL. EAMB treatment decreased EGFR levels, with a 462.9 pg/mL reduction in the combination treatment group, and elevated Caspase 3 levels, reaching 180.2 pg/mL at 443.8 µl/mL after 24 hours. These results demonstrate that EAMB inhibits cell proliferation, reduces EGFR and Ki-67 expression, and enhances apoptosis, suggesting its potential as a therapeutic agent for cervical cancer.
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1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-249. DOI: https://doi.org/10.3322/caac.21660
2. Ministry of Health of the Republic of Indonesia. National Health Research and Development (Riskesdas) Report 2018. Jakarta: Publishing Institution of the Health Research and Development Agency (LPB). 2019: 674.
3. Kumar D, Basu S, Parija L, Rout D, Manna S, Dandapat J. Curcumin and Ellagic acid synergistically induce ROS generation, DNA damage, p53 accumulation and apoptosis in HeLa cervical carcinoma cells. Biomed Pharmacother. 2016;81:31–37. DOI: https://doi.org/10.1016/j.biopha.2016.03.037
4. Singh S, Sharma B, Kanwar SS, Kumar A. Lead phytochemicals for anticancer drug development. Front Plant Sci. 2016;7(11):1–13. DOI: https://doi.org/10.3389/fpls.2016.01667
5. Ubhenin AE, Ikebuiro JO, Idris RI, Anura F, Erharuyi O. Exploring Mechanisms of Tumorigenesis and Plant-Based Therapies: A
Comprehensive Review of Cancer Pathogenesis and Treatment Strategies. Trop J Nat Prod Res. 2023;7(11):5026–5033.
6. Al-Masri AA, Ameen F. Anti-inflammatory effect of anthocyanin-rich extract from banana bract on lipopolysaccharide-stimulated RAW 264.7 macrophages. J Funct Foods. 2023;107(8):1-9. DOI: https://doi.org/10.1016/j.jff.2023.105628
7. Jiang H, Zhang W, Cao J, Jiang W. Development of biodegradable active films based on longan seed starch incorporated with banana flower bract anthocyanin extracts and applications in food freshness indication. Int J Biol Macromol. 2023;251(8):1-16. DOI: https://doi.org/10.1016/j.ijbiomac.2023.126372
8. Mathew NS, Negi PS. Traditional uses, phytochemistry and pharmacology of wild banana (Musa acuminata Colla): A review. J Ethnopharmacol. 2017;196:124-140. DOI: https://doi.org/10.1016/j.jep.2016.12.009
9. Vilhena RO, Figueiredo ID, Baviera AM, Silva DB, Marson BM, Oliveira JA. Antidiabetic activity of Musa x paradisiaca extracts in streptozotocin-induced diabetic rats and chemical characterization by HPLC-DAD-MS. J Ethnopharmacol. 2020;254(1):1-6. DOI: https://doi.org/10.1016/j.jep.2020.112666
10. Lau BF, Kong KW, Leong KH, Sun J, He X, Wang Z. Banana inflorescence: Its bio-prospects as an ingredient for functional foods. Trends Food Sci Technol. 2020;97(3):14-28. DOI: https://doi.org/10.1016/j.tifs.2019.12.023
11. N. Gunavathy, Padmavathy S, Murugavel SC. Phytochemical Evaluation of Musa acuminata Bract Using Screening, Ftir and Uv-Vis Spectroscopic Analysis. J Int Acad Res Multidiscip. 2014;393(1):212–221.
12. Sujithra S, Manikkandan TR. Extraction of Anthocyanin from Banana (Musa paradisiaca) Flower Bract and Analysis of Phytochemicals, Antioxidant Activities and Anthocyanin Content. J Chem Pharm Sci. 2019;12(03):102–104. DOI: https://doi.org/10.30558/jchps.20191203007
13. Roobha J, Saravanakumar M, Aravindhan KM, Suganya devi P. In vitro evaluation of anticancer property of anthocyanin extract from Musa acuminate bract. Res Pharm. 2011;1(4):17–21.
14. Baharara J, Amini E, Vazifedan V. Concomitant Use of Sea Cucumber Organic Extract and Radiotherapy on Proliferation and Apoptosis of Cervical ( HeLa ) Cell Line. Zahedan J Res Med Sci. 2016;18(4):1-6. DOI: https://doi.org/10.17795/zjrms-6442
15. Hasibuan PAZ, Sitorus RKUAB, Hermawan A, Huda F, Waruwu SB, Satria D. Anticancer activity of the ethylacetate fraction of Vernonia amygdalina Delile towards overexpression of HER-2 breast cancer cell lines. Pharmacia. 2024;71:1–8. DOI: https://doi.org/10.3897/pharmacia.71.e125788
16. Pan F, Liu Y, Liu J, Wang E. Stability of blueberry anthocyanin, anthocyanidin and pyranoanthocyanidin pigments and their inhibitory effects and mechanisms in human cervical cancer HeLa cells. RSC Adv. 2019;9(19):10842–10853. DOI: https://doi.org/10.1039/C9RA01772K
17. Newman DJ, Cragg GM. Natural Products as Sources of New Drugs from 1981 to 2014. J Nat Prod. 2016;79(3):629–661. DOI: https://doi.org/10.1021/acs.jnatprod.5b01055
18. Mondal A, Gandhi A, Fimognari C, Atanasov AG, Bishayee A. Alkaloids for cancer prevention and therapy: Current progress and future perspectives. Eur J Pharmacol. 2019;858(6):1-16. DOI: https://doi.org/10.1016/j.ejphar.2019.172472
19. Bossler F, Hoppe-Seyler K, Hoppe-Seyler F. PI3K/AKT/mTOR signaling regulates the virus/host cell crosstalk in HPV-positive cervical cancer cells. Int J Mol Sci. 2019;20(9):1–13. DOI: https://doi.org/10.3390/ijms20092188
20. Qiu J, Hu F, Shao T, Guo Y, Dai Z, Nie H. Blocking of EGFR Signaling Is a Latent Strategy for the Improvement of Prognosis of HPV-Induced Cancer. Front Oncol. 2021;11(9):1–12. DOI: https://doi.org/10.3389/fonc.2021.633794
21. Putri RH, Wasita B, Soetrisno, Priyanto H, Pamungkasari EP, Cilmiaty R. Unveiling Nature’s Treasure: Investigating the Antioxidant and Anticancer Activities of Mas Banana (Musa acuminata Colla) Bracts from Lampung, Indonesia. Trop J Nat Prod Res. 2024;8(8):7984–7989. DOI: https://doi.org/10.26538/tjnpr/v8i8.8
22. Ragab EA, Mohammed AESI, Abbass HS, Kotb SI. A new flavan-3-ol dimer from Ficus spragueana leaves and its cytotoxic activity. Pharmacogn Mag. 2013;9(34):144–148. DOI: https://doi.org/10.4103/0973-1296.111274
23. Krishna A, Sathya M, Mukesh S, Athiyamaan MS, Banerjee S, Sunny J. Efficacy and safety of EGFR inhibitor gefitinib in recurrent or metastatic cervical cancer: a preliminary report. Med Oncol. 2023;40(7):1–6. DOI: https://doi.org/10.1007/s12032-023-02070-1
24. Sigismund S, Avanzato D, Lanzetti L. Emerging functions of the EGFR in cancer. Mol Oncol. 2018;12(1):3–20. DOI: https://doi.org/10.1002/1878-0261.12155
25. Lin BW, Gong CC, Song HF, Cui YY. Effects of anthocyanins on the prevention and treatment of cancer. Br J Pharmacol. 2017;174(11):1226–1243. DOI: https://doi.org/10.1111/bph.13627
26. Lu JN, Lee WS, Kim MJ, Yun JW, Jung JH, Yi SM. The inhibitory effect of anthocyanins on Akt on invasion and epithelial-mesenchymal transition is not associated with the anti-EGFR effect of the anthocyanins. Int J Oncol. 2014;44(5):1756–1766. DOI: https://doi.org/10.3892/ijo.2014.2315
27. Bhattacharjee R, Das SS, Biswal SS, Nath A, Das D, Basu A. Mechanistic role of HPV-associated early proteins in cervical cancer: Molecular pathways and targeted therapeutic strategies. Crit Rev Oncol Hematol. 2022;174:103675. DOI: https://doi.org/10.1016/j.critrevonc.2022.103675
28. Ma L, Yu Y, Qu X. Suppressing serum response factor inhibits invasion in cervical cancer cell lines via regulating egr‑1 and epithelial‑mesenchymal transition. Int J Mol Med. 2019;43(1):614–620. DOI: https://doi.org/10.3892/ijmm.2018.3954
29. Bai Y, Shao Y, Li H, Xue W, Quan F, Wu S. Ki-67 is overexpressed in human laryngeal carcinoma and contributes to the proliferation of HEp2 cells. Oncol Lett. 2016;12(4):2641–2647. DOI: https://doi.org/10.3892/ol.2016.4980
30. Li LT, Jiang G, Chen Q, Zheng JN. Predic Ki67 is a promising molecular target in the diagnosis of cancer (Review). Mol Med Rep. 2015;11(3):1566–1572. DOI: https://doi.org/10.3892/mmr.2014.2914
31. Jing N, Song J, Liu Z, Wang L, Jiang G. Glycosylation of anthocyanins enhances the apoptosis of colon cancer cells by handicapping energy metabolism. BMC Complement Med Ther. 2020;20(1):1–13. DOI: https://doi.org/10.1186/s12906-020-03096-y
32. El-Nashar HAS, Al-Azzawi MA, Al-Kazzaz HH, Alghanimi YK, Kocaebli SM, Alhmammi M. HPLC-ESI/MS-MS metabolic profiling of white pitaya fruit and cytotoxic potential against cervical cancer: Comparative studies, synergistic effects, and molecular mechanistic approaches. J Pharm Biomed Anal. 2024;244(3):1-14. DOI: https://doi.org/10.1016/j.jpba.2024.116121
33. Zhou J, Zhu YF, Chen XY, Han B, Li F, Chen JY. Black rice-derived anthocyanins inhibit HER-2-positive breast cancer epithelial-mesenchymal transition-mediated metastasis in vitro by suppressing FAK signaling. Int J Mol Med. 2017;40(6):1649–1656. DOI: https://doi.org/10.3892/ijmm.2017.3183
34. Gao Y, Tollefsbol TO. Combinational proanthocyanidins and resveratrol synergistically inhibit human breast cancer cells and impact epigenetic–Mediating machinery. Int J Mol Sci. 2018;19(8):1–18. DOI: https://doi.org/10.3390/ijms19082204
35. Lagunas-Rangel FA, Bermúdez-Cruz RM. Natural Compounds That Target DNA Repair Pathways and Their Therapeutic Potential to Counteract Cancer Cells. Front Oncol. 2020;10(11):1–13. DOI: https://doi.org/10.3389/fonc.2020.598174
36. Jang H, Bae WJ, Yuk SM, Han DS, Ha US, Hwang SYl. Seoritae extract reduces prostate weight and suppresses prostate cell proliferation in a rat model of benign prostate hyperplasia. Evidence-based Complement Altern Med. 2014;2:1-7. DOI: https://doi.org/10.1155/2014/475876
37. Natarajan T, Anandhi M, Aiswarya D, Ramkumar R, Kumar S, Perumal P. Idaein chloride induced p53 dependent apoptosis in cervical cancer cells through inhibition of viral oncoproteins. Biochimie. 2016;121:13–20. DOI: https://doi.org/10.1016/j.biochi.2015.11.008
38. Tsai MC, Chen CC, Tseng TH, Chang YC, Lin YJ, Tsai IN. Hibiscus Anthocyanins Extracts Induce Apoptosis by Activating AMP-Activated Protein Kinase in Human Colorectal Cancer Cells. Nutrients. 2023;15(18):1-14. DOI: https://doi.org/10.3390/nu15183972