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http://dx.doi.org/10.7314/APJCP.2014.15.2.963

Asiatic Acid Promotes p21WAF1/CIP1 Protein Stability through Attenuation of NDR1/2 Dependent Phosphorylation of p21WAF1/CIP1 in HepG2 Human Hepatoma Cells  

Chen, Jin-Yuan (Department of General Surgery, Zhujiang Hospital of Southern Medical University)
Xu, Qing-Wen (Department of Gastrointestinal Surgery, Affiliated Hospital of Guangdong Medical College)
Xu, Hong (Department of Pharmacy, Affiliated Hospital of Guangdong Medical College)
Huang, Zong-Hai (Department of General Surgery, Zhujiang Hospital of Southern Medical University)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.15, no.2, 2014 , pp. 963-967 More about this Journal
Abstract
Previous studies have suggested anti-tumor effects of asiatic acid in some human cancer cell lines. This agent is reported to increase the levels of $p21^{WAF1/CIP1}$ in human breast cancer cell lines. However, the molecular mechanisms have not been established. Here we report that asiatic acid up-regulates $p21^{WAF1/CIP1}$ protein expression but not the level of $p21^{WAF1/CIP1}$ mRNA in HepG2 human hepatoma cells. Furthermore, we found that the asiatic acid induced increase of $p21^{WAF1/CIP1}$ protein was associated with decreased phosphorylation (ser-146) of $p21^{WAF1/CIP1}$. Knockdown of NDR1/2 kinase, which directly phosphorylates $p21^{WAF1/CIP1}$ protein at ser-146 and enhances its proteasomal degradation, increased the levels of $p21^{WAF1/CIP1}$ protein and eliminated the regulation of $p21^{WAF1/CIP1}$ stability by asiatic acid. At the same time, the expression of NDR1/2 kinase decreased during treatment with asiatic acid in HepG2 cells. Moreover, asiatic acid inhibited the proliferation of HepG2 cells, this being attenuated by knockdown of $p21^{WAF1/CIP1}$. In conclusion, we propose that asiatic acid inhibits the expression NDR1/2 kinase and promotes the stability of $p21^{WAF1/CIP1}$ protein through attenuating NDR1/2 dependent phosphorylation of $p21^{WAF1/CIP1}$ in HepG2 cells.
Keywords
Asiatic acid; $p21^{WAF1/CIP1}$; stability; NDR1/2; phosphorylation;
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