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Cucurbitacin e induces caspase-dependent apoptosis and protective autophagy mediated by ROS in lung cancer cells
Ma G.1; Luo W.1; Lu J.1; Ma D.-L.2; Leung C.-H.1; Wang Y.1; Chen X.1
2016
Source PublicationChemico-Biological Interactions
Volume253Pages:1
Abstract

Cucurbitacin E (CuE) is a triterpenoid with potent anticancer activities while the underlying mechanisms remain elusive. In the present study, the anticancer effects of CuE on 95D lung cancer cells were investigated. CuE decreased cell viability, inhibited colony formation, and increased reactive oxygen species (ROS) in a concentration-dependent manner, which were reversed by N-acetyl-l-cysteine (NAC). CuE induced apoptosis as determined by JC-1 staining, expression of Bcl-2 family proteins, cleavage of caspases, and TUNEL staining. NAC and Ac-DEVD-CHO partially reversed CuE-induced cleavage of caspase-3, caspase-7, and PARP. Furthermore, CuE caused accumulation of autophagic vacuoles and concentration- and time-dependent expression of LC3II protein. Autophagy inhibitors chloroquine and bafilomycin A1 enhanced CuE-induced LC3II expression and cell death. CuE-triggered protein expression of p-AKT, p-mTOR, Beclin-1, and p-ULK1 was partially reversed by NAC pretreatment. In addition, CuE treatment damaged F-actin without affecting β-tubulin as confirmed by immunofluorescence. In conclusion, CuE induced ROS-dependent apoptosis through Bcl-2 family and caspases in 95D lung cancer cells. Furthermore, CuE induced protective autophagy mediated by ROS through AKT/mTOR pathway. This study provides novel roles of ROS in the anticancer effect of CuE. © 2016 Elsevier Ireland Ltd. All rights reserved.

KeywordApoptosis Autophagy Cancer Cucurbitacin e Reactive Oxygen Species
DOIhttp://doi.org/10.1016/j.cbi.2016.04.028
URLView the original
Indexed BySCI
Language英语
WOS Research AreaBiochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Toxicology
WOS SubjectBiochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Toxicology
WOS IDWOS:000377372800001
The Source to ArticleScopus
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被引频次[WOS]:23   [WOS记录]     [WOS相关记录]
Document TypeJournal article
专题Institute of Chinese Medical Sciences
Corresponding AuthorChen X.
Affiliation1.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Avenida da Universidade, Taipa, Macau, China
2.Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong
First Author AffilicationInstitute of Chinese Medical Sciences
Corresponding Author AffilicationInstitute of Chinese Medical Sciences
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GB/T 7714
Ma G.,Luo W.,Lu J.,et al. Cucurbitacin e induces caspase-dependent apoptosis and protective autophagy mediated by ROS in lung cancer cells[J]. Chemico-Biological Interactions,2016,253:1.
APA Ma G..,Luo W..,Lu J..,Ma D.-L..,Leung C.-H..,...&Chen X..(2016).Cucurbitacin e induces caspase-dependent apoptosis and protective autophagy mediated by ROS in lung cancer cells.Chemico-Biological Interactions,253,1.
MLA Ma G.,et al."Cucurbitacin e induces caspase-dependent apoptosis and protective autophagy mediated by ROS in lung cancer cells".Chemico-Biological Interactions 253(2016):1.
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