Induction of G2/M arrest and apoptosis by water extract of Strychni Semen in human gastric carcinoma AGS cells

• Published in: Phytotherapy research 2008-06, Vol.22 (6), p.752-758
• Main Authors: Lee, Sang Man, Kwon, Jae Im, Choi, Yung Hyun, Eom, Hyun Sup, Chi, Gyoo Yong
• Format: Article
• Language: English
• Subjects: AGS human gastric carcinoma cells; Apoptosis - drug effects; bcl-2-Associated X Protein - genetics; bcl-2-Associated X Protein - metabolism; Biological and medical sciences; Blotting, Western; Caspase 3 - metabolism; Caspase 8 - metabolism; Caspase 9 - metabolism; Cell Cycle - drug effects; Cell Division - drug effects; Cell Line, Tumor; Cyclin A - genetics; Cyclin A - metabolism; Cyclin B - genetics; Cyclin B - metabolism; Cyclin B1; Drugs, Chinese Herbal - chemistry; Drugs, Chinese Herbal - pharmacology; Flow Cytometry; G2 Phase - drug effects; G2/M arrest; General pharmacology; Humans; Medical sciences; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - metabolism; Reverse Transcriptase Polymerase Chain Reaction; Stomach Neoplasms - genetics; Stomach Neoplasms - metabolism; Stomach Neoplasms - pathology; Strychni Semen; Strychnine - chemistry; Strychnine - pharmacology; Strychnos - chemistry; Water - chemistry
• ISSN: 0951-418X; 1099-1573
• DOI: 10.1002/ptr.2355

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.