Document Type
Journal Article
Department/Unit
Department of Chemistry
Title
Cucurbitacin E induces caspase-dependent apoptosis and protective autophagy mediated by ROS in lung cancer cells
Language
English
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.
Keywords
Cucurbitacin E, Reactive oxygen species, Apoptosis, Autophagy, Cancer
Publication Date
6-30-2016
Source Publication Title
Chemico-Biological Interactions
Volume
253
Start Page
1
End Page
9
Publisher
Elsevier
Peer Reviewed
1
DOI
10.1016/j.cbi.2016.04.028
Link to Publisher's Edition
http://dx.doi.org/10.1016/j.cbi.2016.04.028
ISSN (print)
00092797
Recommended Citation
Ma, Guixin, Weiwei Luo, Jinjian Lu, Dik Lung Ma, Chung-Hang Leung, Yitao Wang, and Xiuping Chen. "Cucurbitacin E induces caspase-dependent apoptosis and protective autophagy mediated by ROS in lung cancer cells." Chemico-Biological Interactions 253 (2016): 1-9.