Icariside II inhibits cell proliferation and induces cell cycle arrest through the ROS‑p38‑p53 signaling pathway in A375 human melanoma cells

Wu,Jinfeng; Song,Tao; Liu,Shuyong; Li,Xiaomei; Li,Gang; Xu,Jinhua

doi:10.3892/mmr.2014.2701

Icariside II inhibits cell proliferation and induces cell cycle arrest through the ROS‑p38‑p53 signaling pathway in A375 human melanoma cells

Authors:
- Jinfeng Wu
- Tao Song
- Shuyong Liu
- Xiaomei Li
- Gang Li
- Jinhua Xu
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Affiliations: Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, 200040, P.R. China, Department of Neurosurgery, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 25002, P.R. China, Department of Radiology, Tai'an City Central Hospital, Tai'an, Shandong 271000, P.R. China, Cancer Center, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China
Published online on: October 20, 2014 https://doi.org/10.3892/mmr.2014.2701
Pages: 410-416

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Abstract

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 µM, 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‑α 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.

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