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PTEN activation by DNA damage induces protective autophagy in response to Cucurbitacin B in hepatocellular carcinoma cells
Niu Y.2; Sun W.2; Lu J.-J.2; Ma D.-L.1; Leung C.-H.2; Pei L.3; Chen X.2
2016
Source PublicationOxidative Medicine and Cellular Longevity
ISSN19420994 19420900
Volume2016
Abstract

Cucurbitacin B (Cuc B), a natural product, induced both protective autophagy and DNA damage mediated by ROS while the detailed mechanisms remain unclear. This study explored the mechanism of Cuc B-induced DNA damage and autophagy. Cuc B decreased cell viability in concentration- and time-dependent manners. Cuc B caused long comet tails and increased expression of γ-HAX, phosphorylation of ATM/ATR, and Chk1/Chk2. Cuc B induced autophagy as evidenced by monodansylcadaverine (MDC) staining, increased expression of LC3II, phosphorylated ULK1, and decreased expression of phosphorylated AKT, mTOR. Cuc B induced apoptosis mediated by Bcl-2 family proteins and caspase activation. Furthermore, Cuc B induced ROS formation, which was inhibited by N-acetyl-L-cysteine (NAC). NAC pretreatment dramatically reversed Cuc B-induced DNA damage, autophagy, and apoptosis. Cuc B-induced apoptosis was reversed by NAC but enhanced by 3-methyladenine (3-MA), chloroquine (CQ), and silencing phosphatase and tensin homolog (PTEN). 3-MA and CQ showed no effect on Cuc B-induced DNA damage. In addition, Cuc B increased PTEN phosphorylation and silence PTEN restored Cuc B-induced autophagic protein expressions without affecting DNA damage. In summary, Cuc B induced DNA damage, apoptosis, and protective autophagy mediated by ROS. PTEN activation in response to DNA damage bridged DNA damage and prosurvival autophagy.

DOI10.1155/2016/4313204
URLView the original
Indexed BySCI
Language英语
WOS Research AreaCell Biology
WOS SubjectCell Biology
WOS IDWOS:000390042300001
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Cited Times [WOS]:6   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.Hong Kong Baptist University
2.University of Macau
3.Shanghai University of Traditional Chinese Medicine
First Author AffilicationUniversity of Macau
Recommended Citation
GB/T 7714
Niu Y.,Sun W.,Lu J.-J.,et al. PTEN activation by DNA damage induces protective autophagy in response to Cucurbitacin B in hepatocellular carcinoma cells[J]. Oxidative Medicine and Cellular Longevity,2016,2016.
APA Niu Y..,Sun W..,Lu J.-J..,Ma D.-L..,Leung C.-H..,...&Chen X..(2016).PTEN activation by DNA damage induces protective autophagy in response to Cucurbitacin B in hepatocellular carcinoma cells.Oxidative Medicine and Cellular Longevity,2016.
MLA Niu Y.,et al."PTEN activation by DNA damage induces protective autophagy in response to Cucurbitacin B in hepatocellular carcinoma cells".Oxidative Medicine and Cellular Longevity 2016(2016).
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