Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Combined effect of vorinostat and grape seed proanthocyanidins on modulation of thymidine phosphorylase in non-small cell lung cancer

Yuan-Yuan Wu¹ , Ting-Ting Cao², Chun-Ling Liu¹

¹Department of Medical Oncology; ²Department of Ophthalmology, Cangzhou Central Hospital, Cangzhou 061001, China.

For correspondence:- Yuan-Yuan Wu Email: yuanyuanwu167@gmail.com Tel:+863172079783

Received: 12 February 2015 Accepted: 25 May 2015 Published: 29 June 2015

Citation: Wu Y, Cao T, Liu C. Combined effect of vorinostat and grape seed proanthocyanidins on modulation of thymidine phosphorylase in non-small cell lung cancer. Trop J Pharm Res 2015; 14(6):953-959 doi: 10.4314/tjpr.v14i6.3

© 2015 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

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