标题：Icariside II inhibits cell proliferation and induces cell cycle arrest through the ROS-p38-p53 signaling pathway in A375 human melanoma cells
作者：Wu, Jinfeng;Song, Tao;Liu, Shuyong;Li, Xiaomei;Li, Gang;Xu, Jinhua
作者机构：[Wu, J] Department of Dermatology, Huashan Hospital, Fudan University, 12 Middle Urumqi Road, Shanghai, 200040, China;[ Song, T] Department of Neurosu 更多
通讯作者地址：[Xu, JH]Fudan Univ, Huashan Hosp, Dept Dermatol, 12 Middle Urumqi Rd, Shanghai 200040, Peoples R China.
来源：Molecular medicine reports
关键词：icariside II;melanoma;cell proliferation;reactive oxygen species;p38;p53
摘要：Icariside II (IS) is a metabolite of icariin, which is derived from Herba Epimedii. In the present study, the antiproliferative effects of IS on A375 human melanoma cells were examined in vitro and a possible mechanism through the ROS-p38-p53 pathway is discussed. A cell WST-8 assay revealed that treatment with IS markedly reduced cell viability from 77 to 21% (25 and 100 M, respectively), and cell counting demonstrated that IS treatment reduced cell proliferation. IS treatment also induced cell cycle arrest of A375 cells at the G0/G1 and G2/M transitions and inhibited the expression of cell-cycle related proteins, including cyclin E, cyclin-dependent kinase 2 (CDK2), cyclin B1 and phosphorylated cyclin-dependent kinase 1 (P-CDK1). In this study, it was determined that IS inhibits cell proliferation and induces cell cycle arrest through the generation of reactive oxygen species and activation of p38 and p53. These findings were further supported by the evidence that pretreatment with N-acetyl-L-cysteine, SB203580 or pifithrin- significantly blocked IS-induced reduction of cell viability, increase of cell death and cell cycle arrest. In conclusion, IS inhibits cell proliferation and induces cell cycle arrest. Crucially, it was confirmed that these effects were mediated at least in part by activating the ROS-p38-p53 pathway.