Valproic acid induces autophagy by suppressing the Akt/mTOR pathway in human prostate cancer cells

Qinghua Xia, Yi Zheng, Wei Jiang, Zhongxian Huang, Muwen Wang, Ronald Rodriguez, Xunbo Jin

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Previous studies have demonstrated that the chronic administration of valproic acid (VPA) suppresses angiogenesis in vivo; however, the mechanisms implicated in VPA‑induced autophagy remain unclear. The current study aimed to assess VPA‑induced autophagy in three prostate cancer cell lines (PC3, DU145 and LNCaP), in addition to analyzing the Akt/mammalian target of rapamycin (mTOR) signal pathway. Prostate cancer cell lines were cultured with various doses of VPA. Cell cycle was analyzed using flow cytometry, and autophagy markers [1A/1B‑light chain 3 (LC3)‑II and Beclin‑1] were examined using transmission electron microscopy, fluorescent microscopy and western blotting. Activation of the Akt/mTOR signal pathway was also assessed by western blotting. The results demonstrated that VPA induced autophagosomes and suppressed the Akt/mTOR signal pathway. This was confirmed by detection of increased LC3‑II and Beclin‑1 in VPA‑treated cells compared with untreated controls. Phosphorylated forms of Akt (PC3, P=0.048; DU145, P=0.045; LNCaP, P=0.039) and mTOR (PC3, P=0.012; DU145, P=0.41; LNCaP, P=0.35) were significantly reduced following VPA treatment. These results suggest that VPA may function as a histone deacetylase inhibitor, suppressing the growth of prostate cancer cells by modulating autophagy pathways, including inhibition of the Akt/mTOR pathway. Further experiments are required to determine the significance of all involved pathways regarding VPA‑induced growth inhibition.

Original languageEnglish (US)
Pages (from-to)1826-1832
Number of pages7
JournalOncology Letters
Volume12
Issue number3
DOIs
StatePublished - Sep 2016

Keywords

  • Akt/mammalian target of rapamycin pathway
  • Autophagy
  • Histone deacetylase inhibitor
  • Prostate cancer
  • Valproic acid

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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