Journal of
Cell Biology and Genetics

  • Abbreviation: J. Cell Biol. Genet.
  • Language: English
  • ISSN: 2141-6516
  • DOI: 10.5897/JCBG
  • Start Year: 2010
  • Published Articles: 13

Full Length Research Paper

Blockade of Akt/mTOR pathway and enhancement of histone acetylation by PHI to induce cells apoptosis in prostate cancer PC3 cells

Zhiming Zhuang,
  • Zhiming Zhuang,
  • Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian, 363000, China.
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Xudong Ma
  • Xudong Ma
  • Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian, 363000, China.
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Yiqun Huang
  • Yiqun Huang
  • Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian, 363000, China.
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Zhouda Zheng
  • Zhouda Zheng
  • Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian, 363000, China.
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Yacai Zheng
  • Yacai Zheng
  • Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian, 363000, China.
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Shaohong Jiang
  • Shaohong Jiang
  • Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian, 363000, China.
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  •  Accepted: 01 September 2011
  •  Published: 31 March 2013

Abstract

Mammalian target of rapamycin (mTOR) has merged an important therapeutic target for cancers. Our object is to demonstrate that phenyhexyle isothiocyanate (PHI), a synthetic isothiocyanate, blocked Akt/mTOR signaling in prostate cancer PC3 cell line, in addition to inhibited histone deacetylase to induce cell apoptosis. Apoptotic cells were measured by TUNEL assay. Histone acetylated H3, H4 and the protein of Akt signaling pathway (Akt, p-Akt, mTOR, p-mTOR, p70S6K, p-p70S6K) and apoptosis pathway (caspase-3, caspase-9, MCL-1, Cyt-1, XIAP) were detected by Western Blot. Apoptotic cells were increased after exposure to PHI with a concentration dependent manner. PHI significantly induced an accumulation of histone acetylated H3, H4, as assessed by decreased levels of the phosphorylated (p)-Akt, p-p70 ribosomal S6 kinase (p70S6K) and p-S6K after exposure to PHI for 7 h. The change of proteins of Akt, mTOR, p70S6K was not seen. PHI induced apoptosis through intrinsic pathway. PHI increases histone acetylated H3, H4, which activates gene transcription, induces tumor cell apoptosis. PHI induces Akt dephosphorylation, thus blocking Akt signaling pathway, which is an important therapeutics target.

 

Key words: Phenyhexyle isothiocyanate (PHI), prostate cancer, Akt/mammalian target of rapamycin (mTOR) , histone deacetylase, inhibitor.