A novel dual HDAC6 and tubulin inhibitor, MPT0B451, displays anti-tumor ability in human cancer cells in vitro and in vivo

Yi Wen Wu, Kai Cheng Hsu, Hsueh Yun Lee, Tsui Chin Huang, Tony E. Lin, Yi Ling Chen, Ting Yi Sung, Jing Ping Liou, Wendy W. Hwang-Verslues, Shiow Lin Pan, Wei Chun HuangFu

研究成果: 雜誌貢獻文章

3 引文 斯高帕斯(Scopus)

摘要

The combination cancer therapy is a new strategy to circumvent drug resistance for the treatment of high metastasis and advanced malignancies. Herein, we developed a synthesized compound MPT0B451 that display inhibitory effect against histone deacetylase (HDAC) 6 and tubulin assembly. Our data demonstrated that MPT0B451 significantly inhibited cancer cell growths in HL-60 and PC-3 cells due to inhibition of HDAC activity. MPT0B451 also markedly increased caspase-mediated apoptosis in these cells. The cell cycle analysis showed mitotic arrest induced by MPT0B451 with enhanced expression of G2/M transition proteins. Moreover, molecular docking analysis supported MPT0B451 as a dual HDAC6 and tubulin inhibitor. Finally, MPT0B451 led to tumor growth inhibition (TGI) in HL-60 and PC-3 xenograft models. These findings indicated that MPT0B451 has dual inhibition effects for HDAC6 and tubulin, and also contributed to G2/M arrest followed by apoptotic induction. Together, our results suggested that MPT0B451 may serve as a potent anti-cancer treatment regimen in human prostate cancer and acute myeloid leukemia.
原文英語
文章編號205
期刊Frontiers in Pharmacology
9
發行號MAR
DOIs
出版狀態已發佈 - 三月 13 2018

Keywords

  • Acute myeloid leukemia
  • Apoptosis
  • G2/M arrest
  • HDAC6
  • Microtubule
  • Prostate cancer

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

指紋 深入研究「A novel dual HDAC6 and tubulin inhibitor, MPT0B451, displays anti-tumor ability in human cancer cells in vitro and in vivo」主題。共同形成了獨特的指紋。

  • 引用此