title: Ilexgenin A induces B16-F10 melanoma cell G1/S arrest in vitro and reduces tumor growth in vivo.
abstract: The present study aimed to investigate the anti-tumor activity of Ilexgenin A in B16-F10 murine melanoma and to evaluate its effect on the production of tumor-associated inflammatory cytokines. In vitro, our study showed that Ilexgenin A inhibited the proliferation of B16-F10 murine melanoma cells in a dose- and time-dependent manner, and this effect could be ascribed to the arrest of the cell cycle at G0/G1. In vivo, we evaluated the anti-tumor activity of Ilexgenin A in a tumor-bearing mouse model. The results showed that Ilexgenin A reduced the tumor weight by 51.13% (p<0.01). The Ilexgenin A treatment groups showed no apparent side effects during the treatment period. In addition, a histological analysis revealed that Ilexgenin A changed the cell morphology, and induced large areas of necrosis that correlated with a reduction in tumor size. The detection of inflammatory cytokines indicated that the IL-6 level decreased (p<0.001) and the TNF-α level increased (p<0.01) in mice treated with Ilexgenin A. Ilexgenin A also inhibited the IL-6 production of macrophages stimulated by melanoma conditioned medium (MCM) significantly (p<0.001). Importantly, Ilexgenin A dramatically prolonged survival time (p<0.001). In conclusion, Ilexgenin A could be regarded as a promising agent for the treatment of melanoma; it exerts anti-melanoma activity by arresting the cell cycle at G0/G1 and regulating IL-6 and TNF-α production.
authors.affiliation: Medical and Pharmaceutical Institute, Yangzhou University, 11 Huaihai Road, Yangzhou City, Jiangsu Province 225001, PR China.
authors.forename: Hao
authors.initials: H
authors.lastname: Yang
authors.affiliation: Medical and Pharmaceutical Institute, Yangzhou University, 11 Huaihai Road, Yangzhou City, Jiangsu Province 225001, PR China.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.affiliation: Medical and Pharmaceutical Institute, Yangzhou University, 11 Huaihai Road, Yangzhou City, Jiangsu Province 225001, PR China.
authors.forename: Ya-Qi
authors.initials: YQ
authors.lastname: Zhang
authors.affiliation: Medical and Pharmaceutical Institute, Yangzhou University, 11 Huaihai Road, Yangzhou City, Jiangsu Province 225001, PR China.
authors.forename: Ling-Tian
authors.initials: LT
authors.lastname: Ge
authors.affiliation: Medical and Pharmaceutical Institute, Yangzhou University, 11 Huaihai Road, Yangzhou City, Jiangsu Province 225001, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Medical and Pharmaceutical Institute, Yangzhou University, 11 Huaihai Road, Yangzhou City, Jiangsu Province 225001, PR China.
authors.forename: Xiao-Qin
authors.initials: XQ
authors.lastname: Jia
authors.affiliation: Jiangsu Key Laboratories of Dairy Biological Technology and Safety Control, Yangzhou University, Yangzhou 225127, Jiangsu Province, PR China.
authors.forename: Rui-Xia
authors.initials: RX
authors.lastname: Gu
authors.affiliation: Medical and Pharmaceutical Institute, Yangzhou University, 11 Huaihai Road, Yangzhou City, Jiangsu Province 225001, PR China; Jiangsu Key Laboratories of Dairy Biological Technology and Safety Control, Yangzhou University, Yangzhou 225127, Jiangsu Province, PR China. Electronic address: ysun@yzu.edu.cn.
authors.forename: Yun
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Chinese Medicine Hospital of Yangzhou City, Jiangsu Province 225009, PR China. Electronic address: zyykjc@sina.com.
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Sun
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D030017:Ilex; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008517:Phytotherapy; D018515:Plant Leaves / Q000737:chemistry; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014315:Triterpenes / Q000494:pharmacology* / Q000627:therapeutic use*; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines; D014315:Triterpenes; C468850:ilexgenin A
keywords: B16-F10 murine melanoma cells; Cell cycle arrest; Ilexgenin A; Interleukin-6; Survival time; Tumor necrosis factor-α