 |
|---|
 |
|
|---|
|
 |
|---|
 |
 |
 |
 |
 |
Induction of apoptosis by rhinacanthone isolated from Rhinacanthus nasutus roots in human cervical carcinoma cells.
Siripong P*, Hahnvajanawong C**, Yahuafai J*,
Piyaviriyakul S*,******, Kanokmedhakul K3,Kongkathip N****,
Ruchirawat S*****, Oku N.******
*Natural Products Research Section, Research Division, National Cancer Institute.
**Faculty of Medicine, Khon Kaen University
***Faculty of Science, Khon Kaen University
****Faculty of Science, Kasetsart University
*****Laboratory of Medicinal Chemistry, Chulabhorn Research Institute.
******Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka.
Email: pongpun8@yahoo.com
Abstract
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.
Keywords: rhinacanthone; apoptosis; cervical carcinoma; Rhinacanthus nasutus; mitochondria-dependent signaling pathway
Biological & Pharmaceutical Bulletin Vol. 32 (2009) , No. 7 1251
