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PTEN activation by DNA damage induces protective autophagy in response to Cucurbitacin B in hepatocellular carcinoma cells
Yanan Niu2; Wen Sun2; Jin-Jian Lu2; Dik-Lung Ma1; Chung-Hang Leung2; Lixia Pei3; Xiuping Chen2
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 BySCIE
Language英语
WOS Research AreaCell Biology
WOS SubjectCell Biology
WOS IDWOS:000390042300001
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Cited Times [WOS]:10   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong
2.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Science, University of Macau, Macau
3.Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
First Author AffilicationUniversity of Macau
Recommended Citation
GB/T 7714
Yanan Niu,Wen Sun,Jin-Jian Lu,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 Yanan Niu.,Wen Sun.,Jin-Jian Lu.,Dik-Lung Ma.,Chung-Hang Leung.,...&Xiuping Chen.(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 Yanan Niu,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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