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Research Paper | Biomedical Sciences | Egypt | Volume 6 Issue 7, July 2017

Vorinostat Combined with DNMTi Epigenetically Controls the Proliferation of Lung Cancer Cells A549

Hussein Sabit | Mostafa Fathy | Shimaa E. Abdel-Ghany | Osama A. M. Said | Mokhtar M. El-Zawahry

Abstract: Cancer is being considered one of the fatal diseases in the global population. Lung cancer is one of the most common malignancies in males and in several countries also in females. In the present study, we aimed at evaluating the role of different chemotherapeutic drugs belonging to three groups [Histone Deacetylase Inhibitors (HDACi), DNA Methyltransferase Inhibitors (DNMTi), and Alkylating Agents)]. Vorinostat, Carboplatin, Cyclophosphamide, Temozolomide, and Procaine were applied to A549 lung cancer cells in final concentrations of 3?M and 5?M. Drugs were incubated with the cells for 96 h. Cell viability was measured using Trypan blue exclusion test, and the obtained results showed a significant decrease in the cells' viability after being treated. Global methylation, as an essential epigenetic mark, was quantified in the control and treated cells. The results showed a variation in the methylation patterns, since different combination yielded different methylation profiles. Vorinostat combined with Carboplatin hypomethylated the cells under study, while Vorinostat combined with Cyclophosphamide resulted in hypermethylation of the cells. We concluded that reactivating the hypermethylated genes in the A549 lung cancer cells by combining more than one drug was significantly better than that induced by only one chemotherapeutic agent. However, these results need more confirmatory experiments.

Keywords: Lung Cancer Epigenetics Methylation Vorinostat

Edition: Volume 6 Issue 7, July 2017,

Pages: 855 - 860