Study of autophagy inhibitors and epigenetic drugswithin a cellular line of prostate cancer
Abstract Regulation of epigenetic and autophagy has an important role in prostate cancer. On the one hand, the impact of epigenetic modifications is engaged in proliferation, distinction and tumors survival. Panobinostat is an intense pan-deacetylases inhibitor which can reverse epigenetic changes involved in tumour development. On the other hand, autophagy in starting phases inhibits tumorigenesis endowing anti-oncogenic functions. Nonetheless, in ending phases, spreads metastasis and chemotherapy tolerance. Chloroquine is an antimalarial, it has an antineoplasic effect which is being studying due to its autophagy inhibition. The aim of this project is to assess the cytotoxic effect of Chloroquine and Panobinostat over prostate cellular line VCAP through MTT assay, and analyse the effect of drugs, covering both; concrete and synergistic, over the cellular cycle. Because of the results obtained, it is shown that both drugs cause an antitumor effect in VCAP, being important to point out Panobinostat; it has also been shown that powerful synergetic effect is responsible of death of most cells tumour. To conclude, it would be a good treatment in patients who have been diagnosed with prostate cancer
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Yen C-Y, Huang H-W, Shu C-W, Hou M-F, Yuan S-SF, Wang H-R, et al. DNA methylation, histone acetylation and methylation of epigenetic modifications as a therapeutic approach for cancers. Cancer Lett. 2016; 373(2): 185-92.
Zhang Y, Liao Z, Zhang L, Xiao H. The utility of chloroquine in cancer therapy. Curr Med Res. 2015; 31(5): 1009-13.
Hardy TM, Tollefsbol TO. Epigenetic diet: impact on the epigenome and cancer. Epigenomics. 2011; 3(4): 503-18.
He C, Klionsky DJ. Regulation Mechanisms and Signaling Pathways of Autophagy. Annu Rev Genet. 2009; 43: 67-93.
Kimmelman AC. The dynamic nature of autophagy in cancer. Genes & Development. 2011; 25(19): 1999-2010.
Kouznetsov VV, Amado Torres DF. Antimaláricos: construcción de híbridos moleculares de la cloroquina. Univ Sci. 2008; 13(3): 306-20.
Li X, Zhang J, Xie Y, Jiang Y, Yingjie Z, Xu W. Progress of HDAC inhibitor panobinostat in the treatment of cancer. Curr Drug Targets. 2014; 15(6): 622-34.
Mizushima N, Levine B, Cuervo AM, Klionsky DJ. Autophagy fights disease through cellular self-digestion. Nature. 2008; 451(7182): 1069-75.
Pascolo S. Time to use a dose of Chloroquine as an adjuvant to anti-cancer chemotherapies. Eur J Pharmacol. 2016; 771: 139-44.
Rao R, Balusu R, Fiskus W, Mudunuru U, Venkannagari S, Chauhan L, et al. Combination of pan-histone deacetylase inhibitor and autophagy inhibitor exerts superior efficacy against triple-negative human breast cancer cells. Mol Cancer Ther. 2012; 11(4): 973-83.
Santini V, Gozzini A, Ferrari G. Histone deacetylase inhibitors: molecular and biological activity as a premise to clinical application. Curr Drug Metab. 2007; 8(4): 383-93.
Sharma S, Witteveen PO, Lolkema MP, Hess D, Gelderblom H, Hussain SA, et al. A phase I, open-label, multicenter study to evaluate the pharmacokinetics and safety of oral panobinostat in patients with advanced solid tumors and varying degrees of renal function. Cancer Chemother Pharmacol. 2015; 75(1): 87-95.
Stephenson L. Autophagy in cancer promotes Therapeutic Resistance. Biofiles. 2013; 8(9).
Vaissière T, Sawan C, Herceg Z. Epigenetic interplay between histone modifications and DNA methylation in gene silencing. Mutat Res. 2008; 659(1-2): 40-8.
Yen C-Y, Huang H-W, Shu C-W, Hou M-F, Yuan S-SF, Wang H-R, et al. DNA methylation, histone acetylation and methylation of epigenetic modifications as a therapeutic approach for cancers. Cancer Lett. 2016; 373(2): 185-92.
Zhang Y, Liao Z, Zhang L, Xiao H. The utility of chloroquine in cancer therapy. Curr Med Res. 2015; 31(5): 1009-13.
Sánchez Arroyo, C., & González Sarmiento, R. (2017). Study of autophagy inhibitors and epigenetic drugswithin a cellular line of prostate cancer. FarmaJournal, 2(2), 95–105. Retrieved from https://revistas.usal.es/cinco/index.php/2445-1355/article/view/16017
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