Premium
Induction of G2/M arrest and apoptosis by water extract of Strychni Semen in human gastric carcinoma AGS cells
Author(s) -
Lee Sang Man,
Kwon Jae Im,
Choi Yung Hyun,
Eom Hyun Sup,
Chi Gyoo Yong
Publication year - 2008
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.2355
Subject(s) - cyclin b1 , apoptosis , cyclin dependent kinase 1 , cyclin dependent kinase , cell cycle checkpoint , biology , cyclin a , kinase , microbiology and biotechnology , cell cycle , cancer research , biochemistry
The seed of Strychnos nux‐vomica (Loganiaceae) has been used in traditional Oriental medicine as a folk remedy for the treatment of cancer. However, the mechanism responsible for the anticancer effects of Strychni Semen is not clearly understood. The study tested whether and how the water extract of Strychni Semen (ESS) treatment would affect the growth of AGS human gastric carcinoma cells. ESS was found to inhibit the growth of AGS cells in a concentration‐dependent manner. Cell cycle analysis showed G2/M phase arrest and apoptosis in AGS cells following ESS treatment. ESS‐mediated G2/M arrest was found to be associated with up‐regulation of cyclin A, Cdc2, tumor suppressor p53 and cyclin dependent kinase (Cdk) inhibitor p21(WAF1/CIP1), whereas the expressions of other G2/M regulatory proteins, including cyclin B1 and Cdk2, were down‐regulated compared with the control. The induction of apoptotic cell death by ESS was associated with down‐regulation of anti‐apoptotic Bcl‐2 and up‐regulation of pro‐apoptotic Bax expression. Further results indicate that caspase‐3, caspase‐8 and caspase‐9 are all activated by ESS, together with cleavage of downstream caspase‐3 target proteins. Taken together, the results of this study suggest the involvement of multiple signaling pathways targeted by ESS in mediating G2/M cell cycle arrest and apoptosis in AGS cells, and warrant further investigation. Copyright © 2008 John Wiley & Sons, Ltd.