Astragalus saponins induce growth inhibition and apoptosis in human colon cancer cells and tumor xenograft.
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.
Tin
Mandy M Y
MM
Pharmacology and Toxicology Laboratory, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China.
Cho
Chi-Hin
CH
Chan
Kelvin
K
James
Anthony E
AE
Ko
Joshua K S
JK
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D027883:Astragalus Plant; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D012503:Saponins / Q000008:administration & dosage / Q000494:pharmacology*; D014183:Transplantation, Heterologous; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D012503:Saponins