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Abstract
Introduction: Curcumin is a polyphenol that has pharmacological activity that can inhibit tumor cell growth and induce apoptosis through various mechanisms. However, the specific mechanism of curcumin cytotoxicity remains controversial because of many anti- and pro-apoptotic signaling pathways in various cell types. This study aims to examine the relationship among curcumin on RASSF1A, Bax protein levels, and caspase-3 activity in supporting the apoptotic mechanism in CSA03 breast cancer cells. Method: Curcumin administration to cancer cells is based on differences in dosage with 24-hour incubation. Cytotoxicity after curcumin administration was determined using MTS. RASSF1A and Bax protein levels were tested through ELISA. Caspase-3 activity was used to determine apoptosis and was tested using flow cytometry. Results: The results indicated that curcumin had a cytotoxicity effect of 40.85 µg/mL. At concentrations of 40 µg/mL and 50 µg/mL, curcumin increases levels of protein RASSF1A (∆ = 26.53% and 47.35%, respectively), Bax (∆ = 48.79% and 386.15%), and caspase-3 (∆ = 1,678.51% and 1,871.889%) significantly. Conclusions: Curcumin exhibits anti-proliferative activity and apoptotic (Caspase-3) effects through activation of RASSF1A and Bax.
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References
2. DIRJEN Pelayanan Medik Departemen Kesehatan RI (2010) Kanker di Indonesia tahun 2010: Data Histopatologik. Badan Registrasi Kanker Perhim-punan Dokter Spesialis Patologi Indonesia dan Yayasan Kanker Indonesia.
3. Abdulkareem I, Zurmi I (2012) Review of hormonal treatment of breast cancer. Niger J Clin Pract. 15:9-14. https://doi.org/10.4103/1119-3077.94088
4. Thuy LHA, Thuan LD, Phuong TK DNA hypermeth-ylation in breast cancer. In: Pham PV, ed. (2017) Breast Cancer - From Biology to Medicine. London: InTech. 147-161. https://doi.org/10.5772/66900
5. Cao X, Tang Q, Holland-Letz T, Gündert M, Cuk K, Schott S, Heil J, Golatta M, Sohn C, Schneeweiss A, Burwinkel B (2018) Evaluation of promoter meth-ylation of RASSF1A and ATM in Peripheral blood of breast cancer patients and healthy control individ-uals. Int J Mol Sci. 19:900. https://doi.org/10.3390/ijms19030900
6. Law J, Salla M, Zare A, Wong Y, Luong L, Volodko N, Svystun O, Flood K, Lim J, Sung M, Dyck JRB, Tan CT, Su Y-C, Yu VC, Mackey J, Baksh S (2015) Modu-lator of apoptosis 1 (MOAP-1) is a tumor suppres-sor protein linked to the RASSF1A protein. J Biol Chem. 290:24100-24118. https://doi.org/10.1074/jbc.M115.648345
7. Howell PM, Liu Z, Khong HT (2010) Demethylating agents in the treatment of cancer. Pharmaceuticals (Basel). 3:2022-2044. https://doi.org/10.3390/ph3072022
8. Foulks JM, Parnell KM, Nix RN, Chau S, Swierczek K, Saunders M, Wright K, Hendrickson TF, Ho K-K, McCullar MV, Kanner SB (2012) Epigenetic drug discovery: Targeting DNA methyltransferases. J Bi-omol Screen. 17:2-17. https://doi.org/10.1177/1087057111421212
9. Goel A, Aggarwal BB (2010) Curcumin, the golden spice from Indian saffron, is a chemosensitizer and radiosensitizer for tumors and chemoprotector and radioprotector for normal organs. Nutr Cancer. 62:919-930. https://doi.org/10.1080/01635581.2010.509835
10. Basnet P, Skalko-Basnet N (2011) Curcumin: An anti-inflammatory molecule from a curry spice on the path to cancer treatment. Molecules. 16:4567-4598. https://doi.org/10.3390/molecules16064567
11. Koohpar ZK, Entezari M, Movafagh A, Hashemi M (2015) Anticancer Activity of Curcumin on Human Breast Adenocarcinoma: Role of Mcl-1 Gene. Iran J Cancer Prev. 8:e2331. https://doi.org/10.17795/ijcp2331
12. Rahmah NA, Harliansyah H, Suyatna FD, Kanoko M, Rustamadji P, Prihartono J, Haryono SJ, Hernowo BS (2020) The role of curcumin on apoptosis through the RASSF1A and Bax pathways in breast cancer. Indonesian Journal of Cancer Chemopre-vention. 11:67-74. https://doi.org/10.14499/indonesianjcanchemoprev11iss2pp67-74
13. Hafner M, Niepel M, Chung M, Sorger PK (2016) Growth rate inhibition metrics correct for con-founders in measuring sensitivity to cancer drugs. Nat Methods. 13:521-527. https://doi.org/10.1038/nmeth.3853
14. He Y, Zhu Q, Chen M, Huang Q, Wang W, Li Q, Huang Y, Di W (2016). The changing 50% inhibito-ry concentration (IC50) of cisplatin: A pilot study on the artifacts of the MTT assay and the precise measurement of density-dependent chemo-resistance in ovarian cancer. Oncotarget. 7:70803-70821. https://doi.org/10.18632/oncotarget.12223
15. Nicco C, Batteux F (2017) ROS modulator mole-cules with therapeutic potential in cancers treat-ments. Molecules. 23:84. https://doi.org/10.3390/molecules23010084
16. Skonieczna M, Hejmo T, Poterala-Hejmo A, Cieslar-Pobuda A, Buldak RJ (2017) NADPH oxidases: In-sights into selected functions and mechanisms of action in cancer and stem cells. Oxid Med Cell Lon-gev. 1-15. https://doi.org/10.1155/2017/9420539
17. Lv Z-D, Liu X-P, Zhao W-J, Dong Q, Li F-N, Wang H-B, Kong B (2014) Curcumin induces apoptosis in breast cancer cells and inhibits tumor growth in vitro and in vivo. Int J Clin Exp Pathol. 7:2818-2824.
18. Zhang Y, Cao H, Yu Z, Peng H-Y, Zhang C-J (2013) Curcumin inhibits endometriosis endometrial cells by reducing estradiol production. Iran J Reprod Med. 11:415-422
19. Hagrass HA, Pasha HF, Shaheen MA, Bary EHA, Kassem R (2014) Methylation status and protein expression of RASSF1A in breast cancer patients. Mol Biol Rep. 41:57-65. https://doi.org/10.1007/s11033-013-2837-3
20. Ung M, Ma X, Johnson KC, Christensen BC, Cheng C (2014) Effect of estrogen receptor α binding on functional DNA methylation in breast cancer. Epi-genetics. 9:523-532. https://doi.org/10.4161/epi.27688
21. Cheng Y, Xie N, Jin P, Wang T (2015) DNA methyla-tion and hydroxymethylation in stem cells. Cell Bi-ochem Funct. 33:161-173. https://doi.org/10.1002/cbf.3101
22. Liu Z, Xie Z, Jones W, Pavlovicz RE, Liu S, Yu J, Li P, Lin J, Fuchs JR, Marcucci G, Li C, Chan KK (2009) Curcumin is a potent DNA hypomethylation agent. Bioorg Med Chem Lett. 19:706-709. https://doi.org/10.1016/j.bmcl.2008.12.041