The α-iso-cubebenol compound isolated from Schisandra chinensis induces             p53-independent pathway-mediated apoptosis in hepatocellular carcinoma cells.
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.
Department of Biomaterials Science, College of Natural Resources & Life Science, Pusan National University, Miryang 627-706, Republic of Korea.
Ji Eun
JE
Kim
Sun Guen
SG
Kim
Jun Sue
JS
Goo
Da Jeong
DJ
Park
You Jin
YJ
Lee
In Sik
IS
Hwang
Hae Ryeon
HR
Lee
Sun Il
SI
Choi
Young Ju
YJ
Lee
Chung Hun
CH
Oh
Young Whan
YW
Choi
Dae Youn
DY
Hwang
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms; D010936:Plant Extracts / Q000494:pharmacology*; D032141:Schisandra / Q000737:chemistry*; D012717:Sesquiterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000970:Antineoplastic Agents; C494826:BAX protein, human; D010936:Plant Extracts; D012717:Sesquiterpenes; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C571662:alpha-iso-cubebenol; D051028:bcl-2-Associated X Protein; C505407:CASP3 protein, human; D053148:Caspase 3