The α-iso-cubebenol compound isolated from Schisandra chinensis induces p53-independent pathway-mediated apoptosis in hepatocellular carcinoma cells

Kim,Ji  Eun; Kim,Sun  Guen; Goo,Jun  Sue; Park,Da  Jeong; Lee,You  Jin; Hwang,In  Sik; Lee,Hae  Ryeon; Choi,Sun  Il; Lee,Young  Ju; Oh,Chung  Hun; Choi,Young  Whan; Hwang,Dae  Youn

doi:10.3892/or.2012.1875

The α-iso-cubebenol compound isolated from Schisandra chinensis induces p53-independent pathway-mediated apoptosis in hepatocellular carcinoma cells

Authors:
- Ji Eun Kim
- Sun Guen Kim
- Jun Sue Goo
- Da Jeong Park
- You Jin Lee
- In Sik Hwang
- Hae Ryeon Lee
- Sun Il Choi
- Young Ju Lee
- Chung Hun Oh
- Young Whan Choi
- Dae Youn Hwang
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Affiliations: Department of Biomaterials Science, College of Natural Resources __AMB__ Life Science, Pusan National University, Miryang 627-706, Republic of Korea, Department of Horticultural Bioscience, College of Natural Resources __AMB__ Life Science, Pusan National University, Miryang 627-706, Republic of Korea, School of Dentistry, Dankook University, Cheonan 330-714, Republic of Korea
Published online on: June 19, 2012 https://doi.org/10.3892/or.2012.1875
Pages: 1103-1109

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Abstract

Schisandra chinensis (S. chinensis) plants are extensively used because of their anticancer, anti-inflammatory, antioxidant and antihepatic activities. However, their active compounds remain to be clearly determined. In this study, we investigated the antitumor functions of α-iso-cubebenol (αIC) isolated from S. chinensis using HepG2 hepatocellular carcinoma cells. HepG2 cells were exposed to αIC for 24 h, and apoptosis was assessed using standard viability and cell proliferation assays, flow cytometry and western blotting. HepG2 cell populations treated only with 340 µM of αIC showed markedly increased cell death, but lower concentrations induced minimal alterations of population viability and cell morphology. However, the results of flow cytometry showed that the majority of viable cells were undergoing apoptosis at all tested αIC concentrations. Western blot analysis results revealed a significant and αIC concentration-dependent reduction in the levels of the pro-caspase-3 apoptotic protein and the Bcl-2 anti-apoptotic protein. In particular, the Bax pro-apoptosis protein and p53 (which regulates Bax expression) showed different expression patterns after the application of αIC treatment to HepG2 cells. Bax expression was slightly increased in cells treated with the high concentration of αIC, while p53 expression was markedly reduced in a dose-dependent fashion, similar to that of Bcl-2. The results of this study suggest that αIC is an anticancer drug candidate by virtue of its apoptotic induction abilities in hepatocellular carcinoma cells, which occur via a p53-independent pathway.

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