title: Valproic acid induces autophagy by suppressing the Akt/mTOR pathway in human prostate cancer cells.
abstract: Previous studies have demonstrated that the chronic administration of valproic acid (VPA) suppresses angiogenesisin 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.
authors: Department of Minimally Invasive Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors: Qinghua
authors: Q
authors: Xia
authors: Department of Emergency, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
authors: Yi
authors: Y
authors: Zheng
authors: Department of Minimally Invasive Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors: Wei
authors: W
authors: Jiang
authors: Department of Urology, University of Texas Health Science Center, San Antonio, TX 78229-3900, USA.
authors: Zhongxian
authors: Z
authors: Huang
authors: Department of Minimally Invasive Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors: Muwen
authors: M
authors: Wang
authors: Department of Urology, University of Texas Health Science Center, San Antonio, TX 78229-3900, USA.
authors: Ronald
authors: R
authors: Rodriguez
authors: Department of Minimally Invasive Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors: Xunbo
authors: X
authors: Jin
keywords: Akt/mammalian target of rapamycin pathway; autophagy; histone deacetylase inhibitor; prostate cancer; valproic acid