Betulin induces cytochrome c release and apoptosis in colon cancer cells via NOXA

Betulin is a common triterpene that can be readily obtained from various plants, particularly birch trees, in their natural environment. Specific tumor cells are sensitive to betulin, whereas healthy cells are not. Betulin was observed to stimulate programmed cell death of various cancer cell lines;...

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Bibliographic Details
Published in:Oncology letters 2018-05, Vol.15 (5), p.7319-7327
Main Authors: Zhou, Zhiyuan, Zhu, Chenfang, Cai, Zhongfang, Zhao, Feng, He, Liu, Lou, Xiaolou, Qi, Xiaoliang
Format: Article
Language:English
Subjects:
Apoptosis
Cancer therapies
Care and treatment
Colon cancer
Colorectal cancer
Cytochrome
Cytochrome c
Development and progression
Genetic aspects
Health aspects
Mitochondria
Oncology
Proteins
Terpenes
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Summary:Betulin is a common triterpene that can be readily obtained from various plants, particularly birch trees, in their natural environment. Specific tumor cells are sensitive to betulin, whereas healthy cells are not. Betulin was observed to stimulate programmed cell death of various cancer cell lines; however, the precise molecular mechanism of action of betulin remains unknown. The present study used colon cancer cells, in which mass apoptosis triggered by betulin was identified, and the apoptotic process was demonstrated to occur via the activation of caspase-3 and -9 pathways. In addition, release of cytochrome c was detected. Furthermore, the pro-apoptotic member of the Bcl-2 protein family, NOXA, was induced following treatment with betulin, and the downregulation of NOXA markedly suppressed the release of cytochrome and apoptosis in colon cancer cells. Conversely, the overexpression of NOXA further enhanced betulin-induced apoptosis. The present study therefore offers novel insights into the mechanism of action of the natural compound betulin against tumors.
ISSN:1792-1074
1792-1082
DOI:10.3892/ol.2018.8183