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 (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

指紋

Tubulin Modulators
Histone Deacetylases
Neoplasms
Tubulin
Molecular Docking Simulation
Growth
Caspases
Drug Resistance
Heterografts
Acute Myeloid Leukemia
Prostatic Neoplasms
Cell Cycle
In Vitro Techniques
Apoptosis
Neoplasm Metastasis
Proteins

Keywords

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

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

引用此文

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title = "A novel dual HDAC6 and tubulin inhibitor, MPT0B451, displays anti-tumor ability in human cancer cells in vitro and in vivo",
abstract = "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.",
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author = "Wu, {Yi Wen} and Hsu, {Kai Cheng} and Lee, {Hsueh Yun} and Huang, {Tsui Chin} and Lin, {Tony E.} and Chen, {Yi Ling} and Sung, {Ting Yi} and Liou, {Jing Ping} and Hwang-Verslues, {Wendy W.} and Pan, {Shiow Lin} and HuangFu, {Wei Chun}",
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T1 - A novel dual HDAC6 and tubulin inhibitor, MPT0B451, displays anti-tumor ability in human cancer cells in vitro and in vivo

AU - Wu, Yi Wen

AU - Hsu, Kai Cheng

AU - Lee, Hsueh Yun

AU - Huang, Tsui Chin

AU - Lin, Tony E.

AU - Chen, Yi Ling

AU - Sung, Ting Yi

AU - Liou, Jing Ping

AU - Hwang-Verslues, Wendy W.

AU - Pan, Shiow Lin

AU - HuangFu, Wei Chun

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AB - 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.

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