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 an d 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 apopto tic 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.