Table of Contents
Journal of Cancer Research
Volume 2014 (2014), Article ID 249354, 9 pages
http://dx.doi.org/10.1155/2014/249354
Research Article

BAY 61-3606, CDKi, and Sodium Butyrate Treatments Modulate p53 Protein Level and Its Site-Specific Phosphorylation in Human Vestibular Schwannomas In Vitro

1Department of Human Genetics, NIMHANS, 2900 Hosur Road, Bangalore 560029, India
2Department of Studies in Sericulture/Life Sciences, Jnana Bharathi Campus, Bangalore University, Bangalore 560056, India
3Department of Biotechnology, Bharathiar University, Coimbatore 641046, India
4Department of Neuro Surgery, NIMHANS, Bangalore 560029, India

Received 18 August 2014; Revised 24 September 2014; Accepted 7 October 2014; Published 20 October 2014

Academic Editor: Wenrui Duan

Copyright © 2014 Rohan Mitra et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

This study is done to evaluate the effect of spleen tyrosine kinase inhibitor (BAY 61-3606), cyclin-dependent kinase inhibitor (CDKi), and sodium butyrate (Na-Bu) on the level and phosphorylation of p53 protein and its binding to murine double minute 2 (MDM2) homologue in human vestibular schwannomas (VS). Primary cultures of the tumor tissues were treated individually with optimum concentrations of these small molecules in vitro. The results indicate modulation of p53 protein status and its binding ability to MDM2 in treated samples as compared to the untreated control. The three individual treatments reduced the level of total p53 protein. These treatments also decreased Ser392 and Ser15 phosphorylated p53 in tumor samples of young patients and Ser315 phosphorylated p53 in old patients. Basal level of Thr55 phosphorylated p53 protein was present in all VS samples and it remained unchanged after treatments. The p53 protein from untreated VS samples showed reduced affinity to MDM2 binding in vitro and it increased significantly after treatments. The MDM2/p53 ratio increased approximately 3-fold in the treated VS tumor samples as compared to the control. The differential p53 protein phosphorylation status perhaps could play an important role in VS tumor cell death due to these treatments that we reported previously.