Combined Effect of Vorinostat and Grape Seed Proanthocyanidins on Modulation of Thymidine Phosphorylase in Non-Small Cell Lung Cancer
Purpose: To demonstrate the effect of histone deacetylase-inhibitor, vorinostat, on antitumour activity of grape seed proanthocyanidins (GSPs) in non-small cell lung cancer (NSCLC) cells.
Methods: Expression of thymidine phosphorlase (TP) and thymidylate synthase (TS) was measured by real-time PCR and western blotting. TP knockdown was performed using specific small interfering RNA. Antitumour activity of combination of vorinostat and GSPs was assessed according to Chou and Talay method and by evaluating apoptosis.
Results: Vorinostat treatment led to a significant increase in TP expression but decrease in TS expression in NSCLC cells. In H157 cells, increase in the concentration of vorinostat from 0.34 to 0.4 μM increased TP expression 3- to 6-fold. In H1299 cells, there was 7-fold reduction of TS transcript and 30-fold increase of TP transcript at 48 h. Vorinostat, when used in combination with GSPs, resulted in a synergistic anti-proliferative effect and increased apoptotic cell death. However, cells with TP knockdown did not exhibit vorinostat- and GSPs-mediated anti-proliferative effect and apoptotic cell death.
Conclusion: The combination of vorinostat and GSPs can be an effective and innovative antitumour therapy for the treatment of NSCLC.
Keywords: Histone deacetylase-inhibitor, Synergism, Apoptosis, Antitumor
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