EXPRESSION OF BCL-2 AND BAX GENES INDUCED BY AN OVARIAN EXTRACT OF SINGKARAK LAKE PUFFERFISH (Tetraodon leiurus) IN BREAST CANCER CELL
Keywords:
Cancer, chemoprevention, Jabuih fish, Lake Singkarak, MCF-7 cell lineAbstract
It is known that the ovarian extract of Singkarak Lake Pufferfish (Tetraodon leiurus) has the potential for chemoprevention in MCF-7 cells. However, the expression of Bcl-2 and Bax genes was associated with cancer. Therefore, this study aimed to analyze the Bcl-2 and Bax gene expression induced by the ovarian extract of Singkarak Lake Pufferfish (Tetraodon leiurus) in MCF-7. The method in this study was an in vitro experiment using MCF-7 control cells and MCF-7 cells induced by the ovarian extract of Singkarak Lake Pufferfish (Tetraodon leiurus), and Real-time PCR was used to examine the expression of Bcl-2 and Bax genes. The result showed that the expression of the Bcl-2 gene had an insignificant decrease (p>0.05) by 15%, and the expression of the Bax gene had a significant increase (p<0.05) by 489% compared to the control. These results support that ovarian extract Singkarak Lake Pufferfish (Tetraodon leiurus) can be alternative cancer chemoprevention.
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Adefolaju, G.A., Theron, K.E., & Hosie, M.J. 2015. BAX/BCL-2 mRNA and protein expression in human breast MCF-7 cells exposed to drug vehicles-methanol and dimethyl sulfoxide (DMSO) for 24 hrs. Nigerian medical journal, 56(3): 169–174. DOI: https://doi.org/10.4103/0300-1652.160349
Akbora, D.H., Kunter, I., Erçetin, T., Murat Elagoz, A., & Çiçek, B.A. 2019. Determination of Tetrodotoxin (TTX) Levels in Various Tissues of the Silver Cheeked Puffer Fish (Lagocephalus sceleratus (Gmelin, 1789)) in Northern Cyprus Sea (Eastern Mediterranean). Toxicon, 175: 1-6. DOI: https://doi.org/10.1016/j.toxicon.2019.12.002
Bah, N., Maillet, L., Ryan, J., Dubreil, S., Gautier, F., Letai, A., Juin, P., & Barillé-Nion, S. 2014. Bcl-xL controls a switch between cell death modes during mitotic arrest. Cell Death & Disease, 5(6): 1–11. DOI: https://doi.org/10.1038/cddis.2014.251
Boitano, S., Woodruff, M.L., & Dirksen, E.R. 1997. Reduction of extracellular Na+ causes a release of Ca2+ from internal stores in airway epithelial cells. American Journal of Physiology-Lung Cellular and Molecular Physiology, 272(6): 1189-1197. DOI: https://doi.org/10.1152/ajplung.1997.272.6.L1189
Borhani, N., Manoochehri, M., Gargari, S.S., Novin, M.G., Mansouri, A., & Omrani, M.D. 2014. Decreased Expression of Proapoptotic Genes Caspase-8- and BCL2-Associated Agonist of Cell Death (BAD) in Ovarian Cancer. Clinical Ovarian and Other Gynecologic Cancer, 7(1): 18-23. DOI: https://doi.org/10.1016/j.cogc.2014.12.004
Brown, D.A., Yang, N., & Ray, S.D. 2014. Apoptosis. Encyclopedia of Toxicology: Third Edition. 1: 287–294. DOI: https://doi.org/10.1016/B978-0-12-386454-3.00242-6
Campbell, K., & Haughey, S. 2014. Natural Toxicants: Tetrodotoxin. UK: Queen’s University Belfast. DOI: https://doi.org/10.1016/B978-0-12-378612-8.00186-4
Cao, R., Wang, D., Wei, Q., Wang, Q., Yang, D., Liu, H., Dong, Z., Zhang, X., Zhang, Q., & Zhao, J. 2018. Integrative Biomarker Assessment of the Influence of Saxitoxin on Marine Bivalves: A Comparative Study of the Two Bivalve Species Oysters, Crassostrea gigas, and Scallops, Chlamys farreri. Front. Physiol, 9:1173. DOI: https://doi.org/10.3389/fphys.2018.01173
Chen, C.R., Xia, Y.H., Yao, S.Y., Zhang, Q., Wang, Y., & Ji, Z.N. 2012. Virosecurinine induces apoptosis by affecting Bcl-2 and Bax expression in human colon cancer SW480 cells. Pharmazie, 67(4):351-4.
Chen, G., Jia, Z., Wang, L., & Hu, T. 2020. Effect of acute exposure of saxitoxin on development of zebrafish embryos (Danio rerio). Environmental Research, 185: 109432. DOI: https://doi.org/10.1016/j.envres.2020.109432
Chen, K., Hu, Z., Wang, L.E., Sturgis, E.M., El-Naggar, A.K., Zhang, W., & Wei, Q. 2007. Single-nucleotide polymorphisms at the TP53-binding or responsive promoter regions of BAX and BCL2 genes and risk of squamous cell carcinoma of the head and neck. Carcinogenesis, 28(9): 2008–2012. DOI: https://doi.org/10.1093/carcin/bgm172
Cos, S., Mediavilla, M.D., Fernandez, R., Gonzalez-Lamuno, D., & Sanchez-Barcelo, E.J. 2002. Does melatonin induce apoptosis in MCF-7 human breast cancer cells in vitro. Journal of Pineal Research, 32(2): 90–96. DOI: https://doi.org/10.1034/j.1600-079x.2002.1821.x
Dutordoir, R.M., & Bates, A.D.A. 2016. Activation of apoptosis signaling pathways by reactive oxygen species. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 1863(12): 2977–2992. DOI: https://doi.org/10.1016/j.bbamcr.2016.09.012
Fani, S., Dehghan, F., Karimian, H., Lo, K.M., Nigjeh, E., Keong, Y.S., & Hashim, N.M. 2016. Monobenzyltin Complex C1 Induces Apoptosis in MCF-7 Breast Cancer Cells through the Intrinsic Signaling Pathway and through the Targeting of MCF-7-Derived Breast Cancer Stem Cells via the Wnt/β-Catenin Signaling Pathway. PLOS ONE, 11(8): 1-20. DOI: https://doi.org/10.1371/journal.pone.0160836
Fiebig, A.A., Zhu, W., Hollerbach, C., Leber, B., & Andrews, D.W. 2006. Bcl-XL is qualitatively different from and ten times more effective than Bcl-2 when expressed in a breast cancer cell line. BMC Cancer, 6(1): 1-15. DOI: https://doi.org/10.1186/1471-2407-6-213
Fouda, F.M. 2005. Anti-tumor activity of tetrodotoxin extracted from the masked Pufferfish Arothron diademantus. Egyptian Journal of Biology, 7: 1-13.
Godfrey, L., Kerry, J., Thorne, R., Repapi, E., Davies, J.O.J., Tapia, M., & Milne, T.A. 2017. MLL-AF4 binds directly to a BCL-2 specific enhancer and modulates H3K27 acetylation. Experimental Hematology, 47: 64–75. DOI: https://doi.org/10.1016/j.exphem.2016.11.003
Grigolato, R., Bizzoca, M.E., Calabrese, L., Leuci, S., Mignogna, M.D., & Muzio, L.L. 2020. Leukoplakia and immunology: New chemoprevention landscapes?. International Journal of Molecular Sciences, 21(18): 1–20. DOI: https://doi.org/10.3390/ijms21186874
Guo, J., Lao, Y., & Chang, D.C. 2009. Calcium and Apoptosis. Handbook of Neurochemistry and Molecular Neurobiology, 597–622. DOI: https://doi.org/10.1007/978-0-387-30370-3_33
Hanif, M.M., Putra W.D., Lira, W., Roesma, D.I., & Tjong, D.H. 2021. Antitumor potential of ovarian and skin extract Singkarak Lake Pufferfish (Tetraodon leiurus). International Journal of Biology Research, 6(3): 45-49.
Hata, A.N., Engelman, J.A., & Faber, A.C. 2015. The BCL-2 family: key mediators of the apoptotic response to targeted anti-cancer therapeutics. Cancer Discovery, 5(5): 475–487. DOI: https://doi.org/10.1158/2159-8290.CD-15-0011
Istifli, S.E., Tahir Hüsunet, M., & Basri Ila, H. 2019. Cell Division, Cytotoxicity, and the Assays Used in the Detection of Cytotoxicity. Cytotoxicity - Definition, Identification, and Cytotoxic Compounds, 1–19.
Jagadeeshan, S., Prasad, M.M., & Nair, S.A. 2018. Role of Deguelin in Chemoresistance. In Role of Nutraceuticals in Chemoresistance to Cancer (1st ed., Vol. 2). Elsevier Inc. DOI: https://doi.org/10.1016/B978-0-12-812373-7.00014-0
Kholoussi, N.M., El-Nabi, S.E.H., Esmaiel, N.N., Abd El-Bary, N.M., & El-Kased, A.F. 2014. Evaluation of Bax and Bak gene mutations and expression in breast cancer. BioMed Research International, 1-9. DOI: https://doi.org/10.1155/2014/249372
Ko, E.Y., & Moon, A. 2015. Natural Products for Chemoprevention of Breast Cancer. Journal of Cancer Prevention, 20(4): 223–231. DOI: https://doi.org/10.15430/JCP.2015.20.4.223
Kosker, A.R., Ozogul, F., Durmus, M., Ucar, Y., Ayas, D., Regenstein, J.M., & Ozogul, Y. 2016. Tetrodotoxin level in Pufferfish (Lagocephalus sceleratus) caught in the Northeastern Mediterranean Sea. Food Chemistry, 210: 332-337. DOI: https://doi.org/10.1016/j.foodchem.2016.04.122
Lam, V.K., Nguyen, T.V., Bui, B.M., Chung, L.C., Chang, G., Nehmetallah, G., & Raub, C.B. 2020. Quantitative scoring of epithelial and mesenchymal qualities of cancer cells using machine learning and quantitative phase imaging. Journal of Biomedical Optics, 25(2): 1-17. DOI: https://doi.org/10.1117/1.JBO.25.2.026002
Li, F., Liang, A., Lv, Y., Liu, G., Jiang, A., & Liu, P. 2017. MicroRNA-200c Inhibits Epithelial-Mesenchymal Transition by Targeting the BMI-1 Gene Through the Phospho-AKT Pathway in Endometrial Carcinoma Cells In Vitro. Medical Science Monitor, 23: 5139-5149. DOI: https://doi.org/10.12659/MSM.907207
Li, S., Li, J., Hu, T., Chuhong, Z., Lv, X., He, S., Yan, H., Tan, Y., Wen, M., Lei, M., & Zuo, J. 2017. Bcl-2 overexpression contributes to laryngeal carcinoma cell survival by forming a complex with Hsp90β. Oncology Reports, 37(2): 849–856. DOI: https://doi.org/10.3892/or.2016.5295
Lindeman, G., & Visvader, J.J.E. 2013. Targeting BCL-2 in breast cancer: exploiting a tumor lifeline to deliver a mortal blow?. Breast Cancer Manage, 2(1): 1–4. DOI: https://doi.org/10.2217/bmt.12.60
Liu, Z., Ding, Y., Ye, N., Wild, C., Chen, H., & Zhou, J. 2015. Direct Activation of Bax protein for cancer therapy. Medicinal Research Reviews, 36(2): 313-341. DOI: https://doi.org/10.1002/med.21379
Mansoori, B., Mohammadi, A., Davudian, S., Shirjang, S., & Baradaran B. 2017. The Different Mechanisms of Cancer Drug Resistance: A Brief Review. Advanced Pharmaceutical Bulletin, 7(3): 339–348. DOI: https://doi.org/10.15171/apb.2017.041
Melegari, S.P., Perreault, F., Moukha, S., Popovic, R., Creppy, E.E., & Matias, W.G. 2012. Induction to oxidative stress by saxitoxin investigated through lipid peroxidationin Neuro 2A cells and Chlamydomonas reinhardtiialga. Chemosphere, 89: 38-43. DOI: https://doi.org/10.1016/j.chemosphere.2012.04.009
Mushtaq, S., Abbasi, B.H., Uzair, B., & Abbasi, R. 2018. Natural products as reservoirs of novel therapeutic agents. EXCLI Journal, 17: 420–451.
Pistritto, G., Trisciuoglio, D., Ceci, C., Garufi, A., & D’Orazi, G. 2016. Apoptosis as anti-cancer mechanism: Function and dysfunction of its modulators and targeted therapeutic strategies. Aging, 8(4): 603–619. DOI: https://doi.org/10.18632/aging.100934
Sezer, E.D., Oktay, L.M., Karadadaş, E., Memmedov, H., Selvi Gunel, N., & Sözmen, E. 2019. Assessing Anticancer Potential of Blueberry Flavonoids, Quercetin, Kaempferol, and Gentisic Acid, Through Oxidative Stress and Apoptosis Parameters on HCT-116 Cells. Journal of Medicinal Food, 22(11): 1118-1126. DOI: https://doi.org/10.1089/jmf.2019.0098
Untario, N., Dewi, T., Widodo, M., & Rahaju, P. 2017. Effect of Tetrodotoxin from Crude Pufferfish (Tetraodon fluviatilis) Liver Extract on Intracellular Calcium Level and Apoptosis of HeLa Cell Culture. Journal of Tropical Life Science, 7(1): 23–29. DOI: https://doi.org/10.11594/jtls.07.01.04
Veeruraj, A., Pugazhvendan, S.R., Ajithkumar, T.T., & Arumugam, M. 2016. Isolation and identification of cytotoxic and biological active toxin from the pufferfish Arothron stellatus. Toxicological Research, 32(3): 215–223. DOI: https://doi.org/10.5487/TR.2016.32.3.215
Vijayarathna, S., & Sasidharan, S. 2012. Cytotoxicity of methanol extracts of Elaeis guineensis on MCF-7 and Vero cell lines. Asian Pacific Journal of Tropical Biomedicine, 2(10): 826-829. DOI: https://doi.org/10.1016/S2221-1691(12)60237-8
Walker, J.R., Novick, P.A., Parsons, W.H., McGregor, M., Zablocki, J., Pande, V.S., & Du Bois, J. 2012. Marked difference in saxitoxin and tetrodotoxin affinity for the human nociceptive voltage-gated sodium channel (Nav1.7). Proceedings of the National Academy of Sciences, 109(44): 18102–18107. DOI: https://doi.org/10.1073/pnas.1206952109
Wang, P.G., Li, Y., Pan, Y., Gao, Z.Z., Guan, X.W., Jia, L., & Liu, F.T. 2019. Lower expression of Bax predicts poor clinical outcome in patients with glioma after curative resection and radiotherapy/chemotherapy. Journal of Neuro-Oncology, 141(1): 71–81. DOI: https://doi.org/10.1007/s11060-018-03031-9
Wang, Y., Zhang, L., Yang, J., & Sun, R. 2020. LncRNA KCNQ1OT1 promotes cell proliferation, migration and invasion via regulating miR-129-5p/JAG1 axis in non-small cell lung cancer. Cancer Cell International, 20(144): 1-11. DOI: https://doi.org/10.1186/s12935-020-01225-8
Zhu, H., Yamada, A., Goto, Y., Horn, L., Ngy, L., Wada, M., & Arakawa, O. 2020. Phylogeny and Toxin Profile of Freshwater Pufferfish (Genus Pao) Collected from 2 Different Regions in Cambodia. Toxins, 12(11): 689. DOI: https://doi.org/10.3390/toxins12110689
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