| Literature DB >> 26339399 |
Yuan Xu1, Duo Xu2, Shao-Jun Zhu3, Bing Ye3, Jian-Da Dong3, Yin-Long Zhang3, Yi Zhang3.
Abstract
The present study investigated the effect of valproic acid (VPA) on the inhibition of RET signaling and induction of apoptosis in human thyroid carcinoma cells. VPA inhibited the viability of ARO and WRO cells and also inhibited cyclin D1 and caused caspase-3 cleavage. VPA decreased the level of RET protein and blocked the activation of RET downstream targets including phosphorylated ERK, phosphorylated AKT, and p70S6K/pS6. VPA induced metabolic stress, activated AMP-activated protein kinase and increased autophagic flux. Pharmacological inhibition of autophagy (chloroquine) augmented VPA-inducible cytotoxicity, suggesting that autophagy was protective in VPA-treated cells. VPA has a wide spectrum of activity against human thyroid carcinoma cells, and its cytotoxicity can be augmented by inhibiting autophagy. Expression of VPA molecular targets in metastatic human thyroid carcinoma cells suggests that VPA has a potential to become a thyroid cancer therapeutic agent.Entities:
Keywords: Apoptosis; cytotoxicity; inhibited; metastasis; oxidative stress
Mesh：
Substances：
Year: 2015 PMID： 26339399 PMCID： PMC4555727
Source DB: PubMed Journal: Int J Clin Exp Pathol ISSN： 1936-2625