Evaluation of chloroquine effect in autophagy of breast cancer cells and its possible use in chemotherapy
Abstract Autophagy is a celular mechanism which is in charge of destroying damaged organelles and obtaining nutrients in fasting periods. This process has a very important role in cancer regulation. In early stages of cancer, autophagy prevents the growth of tumoral cells. However, in final stages, it promotes metastasis and resistance to chemotherapy. Chloroquine is an antipaludic drug which, according to recent research, might have antineoplasic properties due to inhibition of autophagy. The target of this research is to prove, in one hand, the citotoxic effect of chloroquine in a breast cancer cell line (BT-549) by performing a MTT assay; and, in the other hand, to study the effect of chloroquine in the expression of three autophagic proteins (LC3, p62 and Beclin-1) using a Western Blot. The results indicate that chloroquine inhibites the growth of tumoral cells at 50 µM and that chloroquine increases the expression of the proteins, which could indicate that chloroquine is inhibiting autophagy. In conclusion, chloroquine might be, in the future, a useful drug in breast cancer chemotherapy.
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Sinha S, Levine B. The autophagy effector Beclin 1: a novel BH3-only protein. Oncogene.2008; 27(1):48-137.
Tanida I, Ueno T, Kominami E. LC3 and Autophagy. Methods Mol Biol. 2008; 445:77-88.
Towbin H, Staehelin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci USA. 1979; 76(9):4350-4.
Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C et al. Cancer Incidence and Mortality Worldwide. Globocan [Revista en Internet] 2012 [acceso 4 de abril de 2015]; 11. Disponible en: http://globocan.iarc.fr.
Jiang PD, Zhao YL, Deng XQ, Mao YQ, Shi W, Tang QQ et al. Antitumor and antimetastatic activities of chloroquine diphosphate in a murine model of breast cancer. Biomed Pharmacother. 2010; 64 (2010): 609–614.
Maycotte P, Thorburn A. Targeting autophagy in breast cancer. World J Clin Oncol. 2014; 5(3): 224-240.
Meerloo JV, Kaspers GJL, Cloos J. Cell Sensitibity Assays: the MTT Assay. En: Cree IA, editor. Cancer Cell Culture: methods in molecular biology. 2ª ed. Portsmouth: Humana Press; 2011. p: 237-245.
Mizushima N, Levine B, Cuervo AM, Klionsky DJ. Autophagy fights disease through cellular self-digestion. Nature. 2008; 451(7182): 1069–1075.
Moscat J, Díaz-Meco MT. P62 at the crossroads of autophagy, apoptosis and cancer. Cell. 2009; 137(6):1001-1004.
Solomon VR, Hoyun Lee H. Chloroquine and its analogs: A new promise of an old drug for effective and safe cancer therapies. Eur J Pharmacol. 2009; 625(2009): 220–233.
Stephenson L. Autophagy in Cancer Promotes Therapeutic Resistance. Biofiles. 2013; 8(9).
Sinha S, Levine B. The autophagy effector Beclin 1: a novel BH3-only protein. Oncogene.2008; 27(1):48-137.
Tanida I, Ueno T, Kominami E. LC3 and Autophagy. Methods Mol Biol. 2008; 445:77-88.
Towbin H, Staehelin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci USA. 1979; 76(9):4350-4.
Orallo, C., & Gonzalez-Sarmiento, R. (2016). Evaluation of chloroquine effect in autophagy of breast cancer cells and its possible use in chemotherapy. FarmaJournal, 1(1), 41–51. Retrieved from https://revistas.usal.es/cinco/index.php/2445-1355/article/view/13227
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