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Chem Biol Interact. 2016 Jun 25;253:1-9. doi: 10.1016/j.cbi.2016.04.028. Epub 2016 Apr 20.

Cucurbitacin E induces caspase-dependent apoptosis and protective autophagy mediated by ROS in lung cancer cells.

Author information

1
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao.
2
Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong.
3
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao. Electronic address: xpchen@umac.mo.

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:

Apoptosis; Autophagy; Cancer; Cucurbitacin E; Reactive oxygen species

PMID:
27106530
DOI:
10.1016/j.cbi.2016.04.028
[Indexed for MEDLINE]

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