Rhinacanthone, a main bioactive
naphthoquinone, isolated from roots of Rhinacanthus nasutus KURZ, (family Acanthaceae), a
Thai traditional medicine, has been reported to possess anticancer effects, although the anticancer mechanism is still unclear. Therefore, we investigated the effects of
rhinacanthone on cell proliferation, cell cycle progression and apoptosis induction in human cervical
carcinoma (HeLa) cells.
beta-Lapachone, an anticancer
drug having a chemical structure related to
rhinacanthone, was used as a positive control. The results demonstrated that
rhinacanthone inhibited proliferation of HeLa cells in a dose-dependent manner and had greater efficacy than that of
beta-lapachone: IC(50) values of the compound ranged from 1.2+/-0.1 to 5.5+/-0.86 muM for 2-24 h time periods.
Rhinacanthone-treated HeLa cells displayed several apoptotic features as evidenced by the appearance of
chromatin condensation, internucleosomal DNA fragmentation, increase in the proportion of sub G(1) apoptotic cells, and externalization of
annexin-V. The apoptotic processes by the treatment with
rhinacanthone involved in a marked increase in the level of
pro-apoptotic protein Bax and decrease in the levels of
anti-apoptotic proteins Bcl-2 and
survivin as well as subsequent activation of
caspase-9 and
caspase-3. Moreover,
rhinacanthone increased the expression of
apoptosis-inducing factor (AIF) which would translocate from mitochondria to nucleus through cytosol, and induce apoptosis through
caspase independent signaling pathway. Taken together, our findings for the first time demonstrate that
rhinacanthone-induced apoptosis in HeLa cells is mediated primarily through the mitochondria-dependent signaling pathway, suggesting that it may be a promising agent for the treatment of human
cervical cancer.