Carcinogenesis Advance Access originally published online on December 5, 2006
Carcinogenesis 2007 28(6):1347-1355; doi:10.1093/carcin/bgl238
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Astragalus saponins induce growth inhibition and apoptosis in human colon cancer cells and tumor xenograft
Pharmacology and Toxicology Laboratory, School of Chinese Medicine, Hong Kong Baptist University, 7 Baptist University Road, Kowloon Tong, Hong Kong, China
1 Department of Pharmacology, Faculty of Medicine, The University of Hong Kong, Hong Kong, China
2 School of Applied Sciences, University of Wolverhampton, Wolverhampton WV1 1SB, UK
3 Laboratory Animal Services Center, The Chinese University of Hong Kong, Hong Kong, China
* To whom correspondence should be addressed. Tel: +852 3411 2907; Fax: +852 3411 2461; Email: jksko{at}hkbu.edu.hk
Astragalus memebranaceus is used as immunomodulating agent in treating immunodeficiency diseases and to alleviate the adverse effects of chemotherapeutic drugs. In recent years, it has been proposed that Astragalus may possess anti-tumorigenic potential in certain cancer cell types. In this study, the anti-carcinogenic effects of Astragalus saponin extract were investigated in HT-29 human colon cancer cells and tumor xenograft. Our findings have shown that Astragalus saponins (AST) inhibit cell proliferation through accumulation in S phase and G2/M arrest, with concomitant suppression of p21 expression and inhibition of cyclin-dependent kinase activity. Besides, AST promotes apoptosis in HT-29 cells through caspase 3 activation and poly(ADP-ribose) polymerase cleavage, which is indicated by DNA fragmentation and nuclear chromatin condensation. Nevertheless, we also demonstrate the anti-tumorigenic effects of AST in vivo, of which the reduction of tumor volume as well as pro-apoptotic and anti-proliferative effects in HT-29 nude mice xenograft are comparable with that produced by the conventional chemotherapeutic drug 5-fluorouracil (5-FU). In addition, the side effects (body weight drop and mortality) associated with the drug combo 5-FU and oxaliplatin are not induced by AST. These results indicate that AST could be an effective chemotherapeutic agent in colon cancer treatment, which might also be used as an adjuvant in combination with other orthodox chemotherapeutic drugs to reduce the side effects of the latter compounds.
Abbreviations: dUTP, 2'-deoxyuridine 5'-triphosphate; PARP, poly(ADP-ribose) polymerase; PCNA, proliferating cell nuclear antigen; TdT, terminal deoxynucleotidyl transferase; TUNEL, terminal deoxynucleotidyl transferase-mediated dUTP in situ nick-end labeling
Received August 21, 2006; revised October 16, 2006; accepted November 19, 2006.