Chemosensitization of oral squamous cell carcinoma cells to cisplatin by histone deacetylase inhibitor, suberoylanilide hydroxamic acid

Hidemi Rikiishi, Fumiaki Shinohara, Tomonori Sato, Yoshitaro Sato, Maiko Suzuki, Seishi Echigo

研究成果: Article査読

61 被引用数 (Scopus)

抄録

In the present study, the precise mechanism of the enhancing action of histone deacetylase (HDAC) inhibitors on cisplatin (CDDP)-induced apoptosis was investigated using suberoylanilide hydroxamic acid (SAHA) in human oral squamous cell carcinoma cells (HSC-3). HDAC inhibitors are promising novel compounds for the treatment of cancer, which cooperate with chemotherapeutic agents to induce apoptosis. Apoptosis enhancement of HSC-3 cells by SAHA was accompanied by the activation of caspase-3, -8 and -9, suggesting a mitochondrial-dependent amplification loop. Concomitant treatment (CDDP/SAHA) of cells resulted in the most effective enhancement of apoptosis compared to other timing combinations. By means of cell-cycle synchronization, G0/G1-phase cells proved to be a more sensitive fraction to SAHA action than their synchronized counterparts in other phases. Furthermore, cells treated with SAHA revealed a decrease in intracellular reduced glutathione (GSH) contents. Of importance, the GSH synthesis inhibitor, diethyl maleate, decreased intracellular GSH and enhanced CDDP-induced apoptosis in a similar pattern of timing to SAHA. Thus, SAHA appears to disrupt the intracellular redox balance, which causes maximal apoptosis at the G0/G1 phase arrested by CDDP in HSC-3 cells. These results demonstrate that HDAC inhibitors not only cause a change in the histone acetylation status, but are also able to influence the apoptotic process at several levels, and GSH plays a key role in governing SAHA-dependent enhancement of CDDP-induced apoptosis.

本文言語English
ページ(範囲)1181-1188
ページ数8
ジャーナルInternational journal of oncology
30
5
DOI
出版ステータスPublished - 2007 5月
外部発表はい

ASJC Scopus subject areas

  • 腫瘍学
  • 癌研究

フィンガープリント

「Chemosensitization of oral squamous cell carcinoma cells to cisplatin by histone deacetylase inhibitor, suberoylanilide hydroxamic acid」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル