PS-341 and Histone Deacetylase Inhibitor Synergistically Induce Apoptosis in Head and Neck Squamous Cell Carcinoma Cells

Overview

Journal Mol Cancer Ther

Date 2010 Jun 24

PMID 20571067

Citations 16

Authors

Jinkoo Kim

Jean Guan

Insoon Chang

Xiaohong Chen

Demin Han

Cun-Yu Wang

Affiliations

Soon will be listed here.

Abstract

Proteasome inhibitor PS-341 (also known as bortezomib) and histone deacetylase (HDAC) inhibitors have emerged as novel therapeutic agents for a variety of malignancies. In this study, we examined whether PS-341 and the HDAC inhibitor trichostatin A (TSA) induced apoptosis in head and neck squamous cell carcinoma (HNSCC), a common and lethal malignancy. We found that, although TSA treatment alone did not induce apoptosis in HNSCC cells, it significantly enhanced PS-341-induced apoptosis in HNSCC cells in vitro. Consistently, TSA significantly improved PS-341-mediated inhibition of HNSCC tumor growth in nude mice. Mechanistically, we found that TSA increased PS-341-induced Noxa expression and caspase activation in HNSCC cells. The knockdown of Noxa significantly reduced apoptosis induced by cotreatment of PS-341 and TSA. Taken together, our results provide new insight into the mechanisms of synergistic antitumor activity of the PS-341 and HDAC inhibitor regimen, offering a new therapeutic strategy for HNSCC patients.

Citing Articles

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