Taxol Effect in Autophagy of Colon Cancer Cells
Abstract Paclitaxel is an anticancer drug used in the treatment of ovarian, breast, non small cell lung, and Kaposi’s sarcoma associated with AIDS. Its mechanism of action is based on blocking ?-tubulin subunit of microtubules, decreasing depolymerisation and stabilizing them; stopping the cell cycle at the G2 / M phase leading to apoptosis.Furthermore, the autophagy, in which process microtubules are very important, is a set of catabolic processes crucial for the maintenance of cell viability; but also is a programmed cell death. The target of this article is to study the drug cytotoxicity and its effect on 6 autophagy related proteins: P62, PKC ?, mTOR, TRAF6, LC3 and Beclin 1; on two colon cancer cell lines: HT29 and HCT-116. The techniques used were the MTT and Western Blot tests. Our results indicate that paclitaxel inhibits the growth of both lines at 10 nM; and increases the expression of Beclin 1, LC3-II and p62 proteins, which indicates an induction of autophagy, and a later block of autolisosoma. In conclusion, we can say that paclitaxel blocks autophagy. Key words: paclitaxel; cáncer; colon; autophagy; p62; LC3-II; Beclin 1.
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Nguyen D, Chen G, Reddy R, Tsai W, Schrump W, Cole G, Schrump D. Potentiation of paclitaxel cytotoxicity in lung and esophageal cancer cells by pharmacologic inhibition of the phosphoinositide 3-kinase/protein kinase B (Akt)–mediated signaling pathway. The journal of thoracic and cardiovascular surgery. 2004; 127(2):365-375.
Peña-Sanoja M, De Sanctis J. Autofagia y respuesta inmunitaria. Investigación clínica. 2013; 54(3):1-13.
Sinha S, Levine B. The autophagy effector Beclin 1: a novel BH3-only protein. Oncogene. 2009; 27(1):137-148.
Towbin H, Staehelin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Nat Acad Sci USA. 1979; 76(9):4350-4354.
Xi G, Hu X, Wub B, Jiang H, Young C, Pang Y, Yuan H. Autophagy inhibition promotes paclitaxel-induced apoptosis in cancer cells. Cancer Letters. 2011; 307:141-148.
Barbuti A, Chen Z. Paclitaxel through the ages of anticancer therapy: exploring its role in chemoresistance and radiation therapy. Cancers. 2015; 7(4):2360-2371.
Ficha técnica de Paclitaxel. Centro Centro de Información online de Medicamentos de la AEMPS – CIMA [base de datos en Internet] Madrid: Agencia Española de Medicamentos y Productos Sanitarios [fecha de acceso: 13 de enero de 2016]. Disponible en: http://www.aemps.gob.es/cima/fichasTecnicas.do?metodo=detalleForm.
Galluzzi F et al. Autophagy in malignant transformation and cancer progression. The EMBO Journal. 2015; 34(4):856-880.
Jiang X, Overholtzer M, Thompson C. Autophagy in cellular metabolism and cancer. Journal of Clinical Investigation. 2015; 125(1):47-54.
Linares J, Duran A, Pasparakis M, Moscat J, Diaz-Meco M. K63 polyubiquitination and activation of mTOR by the p62-TRAF6 complex in nutrient-activated cells. Molecular cell. 2013; 51(3):283-296.
Mathew R, Karp C, Beaudoin B, Vuong N, Chen G, Chen H, Bray K, Reddy A, Bhanot G, Gelinas C, DiPaola R, Karantza-Wadsworth V, Wuite E. Autophagy suppresses tumorigenesis through elimination of p62. Cell. 2009; 137(6):1062-1075
Moscat J, Diaz-Meco M. p62 at the crossroads of autophagy, apoptosis and cancer. Cell. 2009; 137(6):1001-1004.
Mosmann, T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. Journal of Inmunological Methods. 1983; 65(1-2):55-63.
Nguyen D, Chen G, Reddy R, Tsai W, Schrump W, Cole G, Schrump D. Potentiation of paclitaxel cytotoxicity in lung and esophageal cancer cells by pharmacologic inhibition of the phosphoinositide 3-kinase/protein kinase B (Akt)–mediated signaling pathway. The journal of thoracic and cardiovascular surgery. 2004; 127(2):365-375.
Peña-Sanoja M, De Sanctis J. Autofagia y respuesta inmunitaria. Investigación clínica. 2013; 54(3):1-13.
Sinha S, Levine B. The autophagy effector Beclin 1: a novel BH3-only protein. Oncogene. 2009; 27(1):137-148.
Towbin H, Staehelin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Nat Acad Sci USA. 1979; 76(9):4350-4354.
Xi G, Hu X, Wub B, Jiang H, Young C, Pang Y, Yuan H. Autophagy inhibition promotes paclitaxel-induced apoptosis in cancer cells. Cancer Letters. 2011; 307:141-148.
Mateos Temprano, A. M., & González Sarmiento, R. (2017). Taxol Effect in Autophagy of Colon Cancer Cells. FarmaJournal, 2(1), 41–51. Retrieved from https://revistas.usal.es/cinco/index.php/2445-1355/article/view/15146
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