Valproic acid targets HDAC1/2 and HDAC1/PTEN/Akt signalling to inhibit cell proliferation via the induction of autophagy in gastric cancer | Zendy

Sun Jie | Zendy; Piao Junjie | Zendy; Li Nan | Zendy; Yang Yang | Zendy; Kim KiYeol | Zendy; Lin Zhenhua | Zendy

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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 , apoptosis , valproic acid , cancer , protein kinase b , cancer cell , cell growth , chemistry , pi3k/akt/mtor pathway , biology , pharmacology , medicine , histone deacetylase , biochemistry , epilepsy , gene , neuroscience , 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.

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