Continentalic acid from Aralia continentalis induces growth inhibition and apoptosis in HepG2 cells.
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-dependent 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.
Kwon
Tae Oh
TO
Medicinal Resources Research Institute, Wonkwang University, Iksan, 570-749, Korea.
Jeong
Seung-Il
SI
Kwon
Ji Wung
JW
Kim
Youn Chul
YC
Il Jang
Seon
S
D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D027983:Aralia / Q000737:chemistry*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D053938:DNA Fragmentation / Q000187:drug effects; D004224:Diterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D006801:Humans; D007211:Indoles; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D013778:Tetrazolium Salts; D013844:Thiazoles
D000972:Antineoplastic Agents, Phytogenic; D004224:Diterpenes; D005456:Fluorescent Dyes; D007211:Indoles; D011500:Protein Synthesis Inhibitors; D013778:Tetrazolium Salts; D013844:Thiazoles; C510689:continentalic acid; C007293:DAPI; D007770:L-Lactate Dehydrogenase; D053148:Caspase 3; C022616:thiazolyl blue