Journal
ARCHIVES OF PHARMACAL RESEARCH
Volume 31, Issue 9, Pages 1172-1178Publisher
PHARMACEUTICAL SOC KOREA
DOI: 10.1007/s12272-001-1285-3
Keywords
Aralia continentalis; continentalic acid; HepG2 cells; apoptosis
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Funding
- Korean Government [KRF-J03203]
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In this study, we investigated the effects of continentalic acid (CA, (-)-pimara-8(14), 15-diene-19-oic acid), a diterpenic acid, isolated from Aralia continentalis, on the proliferation and apoptosis induction of HepG2 cells. In 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, the inhibitory effect became gradually stronger with the passage of time, 24, 48 and 72 h after treatment with CA, and the most significant effect was observed at 72 h. CA treatment for 72 h induced DNA fragmentation in a dose-dependant manner. Furthermore, flow cytometric analysis of HepG2 cells exposed to CA showed that apoptotic cells increased in a dose-dependent manner. The induction of apoptosis in HepG2 cells by CA was mediated through the activation of caspase-3, Bak, and Bax, and then through the cleavage of peroxisome proliferator-activated receptor (PARP) and the down-regulation of Bcl-2. These results demonstrate that CA efficiently induces apoptosis and is a good candidate for further evaluation as an effective chemotherapeutic agent.
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