Open Access

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

  • Authors:
    • Qinghua Xia
    • Yi Zheng
    • Wei Jiang
    • Zhongxian Huang
    • Muwen Wang
    • Ronald Rodriguez
    • Xunbo Jin
  • View Affiliations

  • Published online on: July 18, 2016     https://doi.org/10.3892/ol.2016.4880
  • Pages: 1826-1832
  • Copyright: © Xia et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.
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September-2016
Volume 12 Issue 3

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Copy and paste a formatted citation
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Spandidos Publications style
Xia Q, Zheng Y, Jiang W, Huang Z, Wang M, Rodriguez R and Jin X: Valproic acid induces autophagy by suppressing the Akt/mTOR pathway in human prostate cancer cells. Oncol Lett 12: 1826-1832, 2016.
APA
Xia, Q., Zheng, Y., Jiang, W., Huang, Z., Wang, M., Rodriguez, R., & Jin, X. (2016). Valproic acid induces autophagy by suppressing the Akt/mTOR pathway in human prostate cancer cells. Oncology Letters, 12, 1826-1832. https://doi.org/10.3892/ol.2016.4880
MLA
Xia, Q., Zheng, Y., Jiang, W., Huang, Z., Wang, M., Rodriguez, R., Jin, X."Valproic acid induces autophagy by suppressing the Akt/mTOR pathway in human prostate cancer cells". Oncology Letters 12.3 (2016): 1826-1832.
Chicago
Xia, Q., Zheng, Y., Jiang, W., Huang, Z., Wang, M., Rodriguez, R., Jin, X."Valproic acid induces autophagy by suppressing the Akt/mTOR pathway in human prostate cancer cells". Oncology Letters 12, no. 3 (2016): 1826-1832. https://doi.org/10.3892/ol.2016.4880