Ilexgenin A induces B16-F10 melanoma cell G1/S arrest in vitro and reduces tumor growth in vivo

• DOI: 10.1016/j.intimp.2014.12.040
• Publication Date: 2015-01-14T03:42:03Z
• Authors: Hao Yang; Chang Liu; Ya-qi Zhang; Ling-tian Ge; Jun Chen; Xiao-qin Jia; Rui-xia Gu; Yun Sun; Wei-dong Sun
• Keywords: Male; Skin Neoplasms; Cell Survival; Macrophages; Cell Cycle; Melanoma, Experimental; Antineoplastic Agents; Ilex; Triterpenes; Cell Line; Tumor Burden; 3. Good health; Mice, Inbred C57BL; Plant Leaves; Mice; 03 medical and health sciences; 0302 clinical medicine; Cell Line, Tumor; Animals; Cytokines; Cell Proliferation; Phytotherapy

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.