Continentalic acid from Aralia continentalis induces growth inhibition and apoptosis in HepG2 cells

  • Arch Pharm Res. 2008 Sep;31(9):1172-8. doi: 10.1007/s12272-001-1285-3.
Tae Oh Kwon  1 Seung-Il Jeong Ji Wung Kwon Youn Chul Kim Seon Il Jang
Affiliations
  • 1. Medicinal Resources Research Institute, Wonkwang University, Iksan, 570-749, Korea.
Abstract

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.

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