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: Hao Yang, Chang Liu, Ya-Qi Zhang, Ling-Tian Ge, Jun Chen, Xiao-Qin Jia, Rui-Xia Gu, Yun Sun, Wei-Dong Sun
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 24 Issue 2 Pg. 423-431 (Feb 2015) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 25596038 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Antineoplastic Agents
• Cytokines
• Triterpenes
• ilexgenin A

Topics

• Animals
• Antineoplastic Agents (pharmacology, therapeutic use)
• Cell Cycle (drug effects)
• Cell Line
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Cytokines (blood, metabolism)
• Ilex
• Macrophages (drug effects, metabolism)
• Male
• Melanoma, Experimental (drug therapy, metabolism, pathology)
• Mice
• Mice, Inbred C57BL
• Phytotherapy
• Plant Leaves (chemistry)
• Skin Neoplasms (drug therapy, metabolism, pathology)
• Triterpenes (pharmacology, therapeutic use)
• Tumor Burden (drug effects)