The histone deacetylase inhibitor trichostatin A induces cell cycle arrest and apoptosis in colorectal cancer cells via p53-dependent and -independent pathways

Oncology Reports
Jin MengQi-Bing Mei

Abstract

Many chemotherapeutic agents induce apoptosis via a p53-dependent pathway. However, up to 50% of human cancers have p53 mutation and loss of p53 function. Histone deacetylase inhibitors (HDACIs) are emerging as a potentially important new class of anticancer agents. Here, we report that, Trichostatin A (TSA), a pan-HDAC inhibitor, could induce G2/M cell cycle arrest and apoptosis in both colorectal cancer cell lines with wild-type p53 (HT116 cells) and mutant p53 (HT29 cells), although HCT116 cells had more apoptotic cells than HT29 cells. TSA induces apoptosis in both cell lines via the mitochondrial pathway as indicated by decrease of the mitochondrial membrane potential (MMP) and activation of caspase-3. Additionally, TSA induces expression of the pro-apoptotic protein Bax and decreases the expression of the anti-apoptotic proteins Bcl-2 and Bcl-xL in both cell lines. Bax knockdown by siRNA significantly impaired TSA-induced apoptosis in both cell lines. These data suggest that TSA induces G2/M cell cycle arrest and Bax-dependent apoptosis in colorectal cancer cells (HCT116 cells and HT29 cells) by both p53-dependent and -independent mechanisms. However, cells with normal p53 function are more sensitive to TSA-induced apopto...Continue Reading

Citations

Jun 8, 2013·World Journal of Gastroenterology : WJG·Yu-Gang WangMin Shi
Jun 13, 2014·Oncology Reports·Magdalena MilczarekJoanna Wietrzyk
Oct 15, 2013·Pathology Oncology Research : POR·Mehdi ManoochehriBahram Kazemi
Nov 19, 2015·International Journal of Molecular Sciences·Ewa MajJoanna Wietrzyk
Aug 21, 2014·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Marco MiceliLucia Altucci
Nov 14, 2016·Cellular Signalling·Claudia SchäferOliver H Krämer
Jun 21, 2014·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Hui YangYi Qiu

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