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Valproic acid targets HDAC1/2 and HDAC1/PTEN/Akt signalling to inhibit cell proliferation via the induction of autophagy in gastric cancer
Author(s) -
Sun Jie,
Piao Junjie,
Li Nan,
Yang Yang,
Kim KiYeol,
Lin Zhenhua
Publication year - 2020
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.15122
Subject(s) - autophagy , pten , cancer research , hdac1 , valproic acid , apoptosis , cancer , protein kinase b , chemistry , pi3k/akt/mtor pathway , pharmacology , biology , medicine , histone deacetylase , epilepsy , biochemistry , neuroscience , gene , histone
Valproic acid (2‐propylpentanoic acid, VPA) has been widely used as an anticonvulsant drug and is a choice drug for seizure treatment. VPA is also used as a short‐chain fatty acid HDAC inhibitor that affects proliferation and differentiation and induces cell apoptosis in both solid and haematologic malignancies. Here, we observed that VPA treatment inhibited HDAC1/2 activity and induced autophagy in gastric cancer cells, leading to apoptosis. VPA‐induced apoptosis occurred through inhibition of the HDAC1/PTEN/Akt signalling pathway and involved alterations in Bcl‐2 and Beclin‐1. The antitumour effects of VPA were verified in vivo using SGC‐7901 xenograft models. Moreover, we evaluated the expression of HDAC1/2 in gastric cancer patient samples and revealed a positive correlation between HDAC1/2 overexpression and poor prognosis. These findings indicate that VPA may serve as a potential therapeutic agent for gastric cancer and that HDAC1/2 might be a promising therapeutic biomarker for the disease.