Anthocyanidins that are reddish pigments widely distributed in fruit and vegetables have been reported to possess
antioxidant and anticancer activities. To understand the molecular basis of the putative anticancer activity of
anthocyanidins, we investigated the antiproliferation effects of
anthocyanidins in human
hepatoma cell lines.
Delphinidin,
cyanidin, and
malvidin exhibited strong growth inhibitory effects against human
hepatoma HepG(2), but were less effective against Hep3B. According to the appearance of the
caspase-3 fragments and stimulated proteolytic cleavage of
poly (ADP-ribose) polymerase (PARP) in time-dependent studies,
delphinidin induced apoptotic cell death characterized by internucleosomal DNA fragmentation and caused a rapid induction of
caspase-3 activity. RT-PCR and Western blot data revealed that
delphinidin stimulated an increase in the c-Jun and JNK phosphorylation expression at
mRNA and
protein levels, respectively. Moreover,
delphinidin-induced apoptotic cell death was accompanied by up-regulation of Bax and down-regulation of Bcl-2
protein. Dephinidin-induced DNA fragmentation was blocked by
N-acetyl-l-cysteine and
catalase, suggesting that the death signaling was triggered by oxidative stress. Our experiments provide evidence that
delphinidin is an effective apoptosis inducer in HepG(2) cells through regulation of Bcl-2 family moleculars and activation of
c-Jun N-terminal kinase cascade. The results suggest that induction of apoptosis by
anthocyanidins is a pivotal mechanism of their
cancer chemopreventive functions.