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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

Authors
 Jie Sun  ;  Junjie Piao  ;  Nan Li  ;  Yang Yang  ;  Ki‐Yeol Kim  ;  Zhenhua Lin 
Citation
 FEBS JOURNAL, : epub., 2019 
Journal Title
 FEBS JOURNAL 
ISSN
 1742-464X 
Issue Date
2019
Keywords
HDAC ; HDAC1/PTEN/Akt ; VPA ; antitumour agent
Abstract
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.
Full Text
https://febs.onlinelibrary.wiley.com/doi/full/10.1111/febs.15122
DOI
10.1111/febs.15122
Appears in Collections:
2. College of Dentistry (치과대학) > Others (기타) > 1. Journal Papers
Yonsei Authors
Kim, Ki Yeol(김기열) ORCID logo https://orcid.org/0000-0001-5357-1067
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/175676
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