Histone deacetylase inhibitor trichostatin A inhibits the growth of bladder cancer cells through induction of p21WAF1 and G1 cell cycle arrest
- 1 May 2006
- journal article
- Published by Wiley in International Journal of Urology
- Vol. 13 (5), 581-586
- https://doi.org/10.1111/j.1442-2042.2006.01344.x
Abstract
To investigate whether Trichostatin A (TSA) possesses antitumor activity against human bladder cancer cells, and if any, its mechanism. A human bladder cancer cell line, BIU-87, was treated with different concentrations of TSA. After treatment, cell growth was measured by MTT assay. Cell apoptosis and cell cycle changes were examined by means of flow cytometry (FCM). Apoptosis was confirmed by apoptotic ladder formation assay. mRNA expression of p21WAF1 and p53 was assessed by differential reverse transcription-polymerase chain reaction. Trichostatin A significantly inhibited the proliferation of bladder cancer cell at nanomolar concentrations in a time- and dose-dependent fashion. TSA treatment caused cell cycle arrest at the G1 phase and increased apoptotic cell death as shown by FCM and DNA fragmentation analysis, accompanied by increased p21WAF1 mRNA expression. In addition, TSA treatment did not alter p53 mRNA expression. Our results indicate that TSA is able to inhibit bladder cancer cell growth in vitro, possibly through p21WAF1 mediated cell cycle arrest and apoptotic cell death. This study suggests that TSA may be a potential therapeutic agent for the treatment of bladder cancer.Keywords
This publication has 25 references indexed in Scilit:
- P21WAF1/CIP1 is dispensable for G1 arrest, but indispensable for apoptosis induced by sodium butyrate in MCF-7 breast cancer cellsOncogene, 2004
- Trichostatin A, an inhibitor of histone deacetylases, strongly suppresses growth of pancreatic adenocarcinoma cellsMolecular Carcinogenesis, 2003
- Downregulation of p21waf/cip-1 mediates apoptosis of human hepatocellular carcinoma cells in response to interferon-γExperimental Cell Research, 2003
- Overexpression of p21Waf1 Induces Apoptosis in Immortalized Human Vascular Smooth Muscle Cells.Journal of Atherosclerosis and Thrombosis, 2003
- Induction and superinduction of growth arrest and DNA damage gene 45 (GADD45) α and β messenger RNAs by histone deacetylase inhibitors trichostatin A (TSA) and butyrate in SW620 human colon carcinoma cellsCancer Letters, 2002
- p21 Waf1/Cip1 can protect human colon carcinoma cells against p53-dependent and p53-independent apoptosis induced by natural chemopreventive and therapeutic agentsOncogene, 2001
- The Human Histone Deacetylase FamilyExperimental Cell Research, 2001
- Requirement for p53 and p21 to Sustain G 2 Arrest After DNA DamageScience, 1998
- Involvement of histone hyperacetylation in triggering DNA fragmentation of rat thymocytes undergoing apoptosisFEBS Letters, 1996
- Trichostatin A and trapoxin: Novel chemical probes for the role of histone acetylation in chromatin structure and functionBioEssays, 1995