Shah , R.D and Jagtap , J.C and Mruthyunjaya , S and Shelke , G.V and Pujari , R and Das , G. and Shastry, P. (2013) Sodium Valproate Potentiates Staurosporine-Induced Apoptosis in Neuroblastoma Cells Via Akt/Survivin Independently of HDAC Inhibition. Journal of Cellular Biochemistry , 114. pp. 854-863.

Full text not available from this repository. (Request a copy)

Abstract

Sodium valproate (VPA) has been recently identified as a selective class I histone deacetylase (HDAC) inhibitor and explored for its potential as an anti-cancer agent. The anti-cancer properties of VPA are generally attributed to its HDAC inhibitory activity indicating a clear overlap of these two actions, but the underlying mechanisms of its anti-tumor effects are not clearly elucidated. The present study aimed to delineate the molecular mechanism of VPA in potentiating cytotoxic effects of anti-cancer drugs with focus on inhibition of HDAC activity. Using human neuroblastoma cell lines, SK-N-MC, SH-SY5Y, and SK-N-SH, we show that non-toxic dose (2 mM) of VPA enhanced staurosporine (STS)- induced cell death as assessed by MTT assay, PARP cleavage, hypodiploidy, and caspase 3 activity. Mechanistically, the effect of VPA was mediated by down regulation of survivin, an anti-apoptotic protein crucial in resistance to STS-mediated cytotoxicity, through Akt pathway. Knock down of class I HDAC isoforms remarkably inhibited HDAC activity comparable with that of VPA but had no effect on STS-induced apoptosis. Moreover, MS-275, a structurally distinct class I HDAC inhibitor did not affect STS-mediated apoptosis, nor decrease the levels of survivin and Akt. Valpromide (VPM), an amide analog of VPA that does not inhibit HDAC also potentiated cell death in NB cells associated with decreased survivin and Akt levels suggesting that HDAC inhibition might not be crucial for STS-induced apoptosis. The study provides new information on the possible molecular mechanism of VPA in apoptosis that can be explored in combination therapy in cancer.

Item Type:	Article
Subjects:	Cancer Biology
Depositing User:	Mr. Rameshwar Nema
Date Deposited:	13 Apr 2015 05:43
Last Modified:	03 Jul 2015 05:08
URI:	http://nccs.sciencecentral.in/id/eprint/49

Actions (login required)

View Item