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 c 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.