Cbl-b-regulated extracellular signal-regulated kinase signaling is involved in the shikonin-induced apoptosis of lung cancer cells in vitro

Qu,Dan; Chen,Yu; Xu,Xiao-Man; Zhang,Meng; Zhang,Yi; Li,Sheng-Qi

doi:10.3892/etm.2015.2283

Cbl-b-regulated extracellular signal-regulated kinase signaling is involved in the shikonin-induced apoptosis of lung cancer cells in vitro

Authors:
- Dan Qu
- Yu Chen
- Xiao-Man Xu
- Meng Zhang
- Yi Zhang
- Sheng-Qi Li
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Affiliations: Department of Respiratory Medicine, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China, Department of Geriatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China
Published online on: February 10, 2015 https://doi.org/10.3892/etm.2015.2283
Pages: 1265-1270

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Abstract

Shikonin (SK), a naturally occurring naphthoquinone, exhibits antitumor activity. However, its precise mechanisms of action are unknown. In the present study, the effects of SK on NCI‑H460 human lung cancer cells were investigated. It was found that SK reduced cell viability and induced apoptosis in the NCI‑H460 cells. Additionally, SK inhibited extracellular signal‑regulated kinase (ERK) activity, which indicates that inhibition of the ERK pathway is probably one of the mechanisms by which SK induced NCI‑H460 cell apoptosis. The expression of Cbl‑b was significantly increased by treatment with SK for 4 h, and gradually increased to a maximal level at 24 h; the time taken for the upregulation of Cbl‑b protein was in accordance to that required for the downregulation of phospho (p)‑ERK protein. The Cbl inhibitor Ps341 reversed the SK‑induced downregulation of p‑ERK and apoptosis of NCI‑H460 cells. These results indicate that Cbl‑b potentiates the apoptotic action of SK by inhibiting the ERK pathway in lung cancer cells.

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