Asparanin A induces G(2)/M cell cycle arrest and apoptosis in human hepatocellular carcinoma HepG2 cells.

Abstract

We recently established that asparanin A, a steroidal saponin extracted from Asparagus officinalis L., is an active cytotoxic component. The molecular mechanisms by which asparanin A exerts its cytotoxic activity are currently unknown. In this study, we show that asparanin A induces G(2)/M phase arrest and apoptosis in human hepatocellular carcinoma HepG2 cells. Following treatment of HepG2 cells with asparanin A, cell cycle-related proteins such as cyclin A, Cdk1 and Cdk4 were down-regulated, while p21(WAF1/Cip1) and p-Cdk1 (Thr14/Tyr15) were up-regulated. Additionally, we observed poly (ADP-ribose) polymerase (PARP) cleavage and activation of caspase-3, caspase-8 and caspase-9. The expression ratio of Bax/Bcl-2 was increased in the treated cells, where Bax was also up-regulated. We also found that the expression of p53, a modulator of p21(WAF1/Cip1) and Bax, was not affected in asparanin A-treated cells. Collectively, our findings demonstrate that asparanin A induces cell cycle arrest and triggers apoptosis via a p53-independent manner in HepG2 cells. These data indicate that asparanin A shows promise as a preventive and/or therapeutic agent against human hepatoma.

• Authors: Wei Liu, Xue-Feng Huang, Qi Qi, Qin-Sheng Dai, Li Yang, Fei-Fei Nie, Na Lu, Dan-Dan Gong, Ling-Yi Kong, Qing-Long Guo
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 381 Issue 4 Pg. 700-5 (Apr 17 2009) ISSN: 1090-2104 [Electronic] United States
• PMID: 19254688 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• CDKN1A protein, human
• Cyclin-Dependent Kinase Inhibitor p21
• Saponins
• asparanin A
• CDC2 Protein Kinase
• Cyclin-Dependent Kinase 2

Topics

• Antineoplastic Agents, Phytogenic (pharmacology, therapeutic use)
• Apoptosis
• Asparagus Plant (chemistry)
• CDC2 Protein Kinase (metabolism)
• Carcinoma, Hepatocellular (drug therapy, metabolism, prevention & control)
• Cell Cycle (drug effects)
• Cell Division (drug effects)
• Cell Line, Tumor
• Cyclin-Dependent Kinase 2 (metabolism)
• Cyclin-Dependent Kinase Inhibitor p21 (metabolism)
• G2 Phase (drug effects)
• Humans
• Liver Neoplasms (drug therapy, metabolism, prevention & control)
• Saponins (pharmacology, therapeutic use)