Histone deacetylase inhibitor trichostatin A inhibits the growth of bladder cancer cells through induction of p21^WAF1 and G₁ cell cycle arrest

Abstract

Purpose: To investigate whether Trichostatin A (TSA) possesses antitumor activity against human bladder cancer cells, and if any, its mechanism. Materials and methods: 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 p21 WAF1 and p53 was assessed by differential reverse transcription-polymerase chain reaction. Results: 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 G 1 phase and increased apoptotic cell death as shown by FCM and DNA fragmentation analysis, accompanied by increased p21 WAF1 mRNA expression. In addition, TSA treatment did not alter p53 mRNA expression. Conclusion: Our results indicate that TSA is able to inhibit bladder cancer cell growth in vitro, possibly through p21 WAF1 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.

Effect of Trans-2,3-Dimethoxycinnamoyl Azide on Enhancing Antitumor Activity of Romidepsin on Human Bladder Cancer

“…In our study, romidepsin inhibits TCC cell growth by inducing both G 1 -S cell cycle arrest and apoptosis (Fig. 2); these results are consistent with other reports showing that HDACIs caused cell cycle arrest at the G 1 phase and increased apoptosis (25,26). Noticeably, DMCA can enhance the romidepsin effect and result in more G 1 -S cell cycle arrest and apoptosis.…”

Regulation of histone acetylation by NDRG2 in glioma cells

“…Other studies showed that TSA upregulated p21 and Bax expression and induced glioma cells to undergo apoptosis [14,15]. In the current study, we demonstrated that TSA upregulated the expression of NDRG2 and that acetyl-H3/H4 and NDRG2 knockdown blocked TSA-induced histone acetylation.…”

Apoptosis of bladder cancer by sodium butyrate and cisplatin

“…Similarly, the HDACi trichostatin A (TSA) has been reported to cause arrest of the cell cycle by increasing expression of p21 [27]. TSA is not an anticancer drug, but has been shown to induce arrest of the cell cycle at G 1 and G 2 and to inhibit proliferation of several cancer cell lines [10,11,16,28].…”

“…Although several studies have shown the effects of HDACis [16,17], as well as combination therapy of HDACis and chemotherapeutic agents [18] on bladder cancer cell lines, the precise mechanism of action of these drugs has not been established. In this study, using sodium butyrate (SB), an HDACi, in combination with CDDP, growth inhibition and cell-cycle analysis, including induction of apoptosis in human bladder cancer cells, were analyzed by XTT assay and laser scanning cytometry (LSC), respectively.…”