Asparanin A induces G(2)/M cell cycle arrest and apoptosis in human hepatocellular carcinoma HepG2 cells.
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.
Liu
Wei
W
Department of Physiology, China Pharmaceutical University, Nanjing, People's Republic of China.
Huang
Xue-Feng
XF
Qi
Qi
Q
Dai
Qin-Sheng
QS
Yang
Li
L
Nie
Fei-Fei
FF
Lu
Na
N
Gong
Dan-Dan
DD
Kong
Ling-Yi
LY
Guo
Qing-Long
QL
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis; D027761:Asparagus Plant / Q000737:chemistry; D016203:CDC2 Protein Kinase / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism* / Q000517:prevention & control; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000517:prevention & control; D012503:Saponins / Q000494:pharmacology* / Q000627:therapeutic use
D000972:Antineoplastic Agents, Phytogenic; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D012503:Saponins; C540172:asparanin A; D016203:CDC2 Protein Kinase; D051357:Cyclin-Dependent Kinase 2