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Article 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 / Copyright

    Affiliations: Department of Minimally Invasive Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China, Department of Emergency, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China, Department of Urology, University of Texas Health Science Center, San Antonio, TX 78229-3900, USA
    Copyright: © Xia et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1826-1832
    |
    Published online on: July 18, 2016
       https://doi.org/10.3892/ol.2016.4880
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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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Copy and paste a formatted citation
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
Copy and paste a formatted citation
x
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
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