title: Anti-colorectal cancer activity of macrostemonoside A mediated by reactive oxygen species.
abstract: Macrostemonoside A (MSS.A), an active steroidal saponin from Allium macrostemon Bung has been shown to possess anti-coagulation and anti-obesity effects. However, the functional role of MSS.A on tumor growth has not been elucidated. We found that MSS.A significantly inhibited human colorectal cancer cell growth in Caco2 and SW480 cells. Incubation of SW480 cells with MSS.A for 48 h resulted in cell cycle arrest. Moreover, MSS.A dose-dependently induced apoptosis in SW480 cells as shown by increased AnnexinV positively stained cell population, caspase activation, increased pro-apoptotic and reduced anti-apoptotic Bcl-2 family protein levels. Treatment of SW480 cells with MSS.A resulted in increased reactive oxygen species (ROS) generation. However, pre-incubation of SW480 cells with antioxidant N-acetylcysteine (NAC) attenuated the ROS generation and anti-colorectal cancer activities of MSS.A. Lastly, intra-peritoneal injections of MSS.A significantly inhibited tumor formation in BALB/c nude mice carcinogenesis xenograft model by reduced tumor volume and tumor weight when treated at dosages of 10, 50 or 100mg/kg daily for 35 days compared with PBS control. Taken together, our results indicate that MSS.A suppressed colorectal cancer growth and induced cell apoptosis by inducing ROS production, and that MSS.A may have therapeutic relevance in the treatment of human colorectal cancer.
authors.affiliation: Department of Colorectal Surgery, The Third Affiliated Hospital of Harbin Medical University, 150 Haping Road, 150081 Harbin, China.
authors.forename: Yihui
authors.initials: Y
authors.lastname: Wang
authors.forename: Qingchao
authors.initials: Q
authors.lastname: Tang
authors.forename: Shixiong
authors.initials: S
authors.lastname: Jiang
authors.forename: Mingqi
authors.initials: M
authors.lastname: Li
authors.forename: Xishan
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D018938:Caco-2 Cells; D063646:Carcinogenesis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012503:Saponins / Q000737:chemistry / Q000627:therapeutic use*; D013256:Steroids / Q000737:chemistry / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004365:Drugs, Chinese Herbal; D017382:Reactive Oxygen Species; D012503:Saponins; D013256:Steroids; C080645:macrostemonoside A
keywords: AFC; Colorectal cancer; MSS.A; Macrostemonoside A; N-acetylcysteine; NAC; PCNA; PI; ROS; Reactive oxygen species; aminofluorocoumarin; macrostemonoside A; proliferating cell nuclear antigen; propidium iodide; reactive oxygen species