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Research Paper
Growth Arrest Induced by C75, A Fatty Acid Synthase Inhibitor, Was Partially Modulated by p38 MAPK but not by p53 in Human Hepatocellular Carcinoma
Yan Gao, Li-Ping Lin, Cai-Hua Zhu, Fa-jun Nan, Xiong-Wen Zhang, Yi Chen, Yong-Tai Hou and Jian Ding
volume 5 | issue 8
august 2006Pages: 978 - 985
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C75, a well known fatty acid synthase (FAS) inhibitor, has been shown to possess potent anti-cancer activity in vitro and in vivo. In this study, we reveal that C75 is a cell cycle arrest inducer and explore the potential mechanisms for this effect in hepatocellular carcinoma (HCC) cell lines with abundant FAS expression: HepG2 and SMMC7721 cells with wt-p53, and Hep3B cells with null p53. The results showed FAS protein expression and basal activity levels were higher in HepG2 cells than in the other two HCC cell lines. Treatment with C75 inhibited FAS activity within 30 min of administration and induced G2 phase arrest accompanied by p53 overexpression in HepG2 and SMMC7721 cells. By contrast, C75 triggered G1 phase arrest in Hep3B cells, and RNA interference targeting p53 did not attenuate C75-induced G2 arrest in HepG2 cells. Similarly, p53 over-expresssion via p53 plasmid transfection did not affect C75-induced G1 phase arrest in Hep3B cells. However, we observed a clear correlation between p38 MAPK activation triggered by C75 and the induction of cell cycle arrests in all three HCC cells. Furthermore, treatment with the p38 MAPK inhibitor SB203580 reduced p38 MAPK activity and cell cycle arrest, and also partially restored cyclin A, cyclin B1, cyclin D1 and p21 protein levels. Collectively, it was p38 MAPK but not p53 involved in C75-mediated tumor cell growth arrest in HCC cells.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.