title: Induction of apoptosis by rhinacanthone isolated from Rhinacanthus nasutus roots in human cervical carcinoma cells.
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.
authors: Natural Products Research Section, Research Division, National Cancer Institute. pongpun8@yahoo.com
authors: Pongpun
authors: P
authors: Siripong
authors: Chariya
authors: C
authors: Hahnvajanawong
authors: Jantana
authors: J
authors: Yahuafai
authors: Suratsawadee
authors: S
authors: Piyaviriyakul
authors: Kwanjai
authors: K
authors: Kanokmedhakul
authors: Ngampong
authors: N
authors: Kongkathip
authors: Somsak
authors: S
authors: Ruchirawat
authors: Naoto
authors: N
authors: Oku
mesh_terms: D027901:Acanthaceae / Q000737:chemistry*; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis / Q000235:genetics; D001578:Benzopyrans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D009285:Naphthoquinones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; D001578:Benzopyrans; D009285:Naphthoquinones; C420690:rhinacanthone