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

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

doi:10.3892/etm.2015.2283

Dan Qu, Sheng-Qi Li + Show 4 more

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https://doi.org/10.3892/etm.2015.2283

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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.

Highlights

Lung cancer is the leading cause of cancer mortality worldwide
To determine whether SK inhibits the proliferation of lung cancer cells, NCI‐H460 cells were treated with different concentrations of SK (0.312‐10 μM) for 24 or 48 h
extracellular signal‐regulated kinase (ERK) is associated with the mitogen‐activated protein kinase (MAPK) pathway; it plays an important role in tumor incidence and development by inducing tumor cell differentiation and proliferation

Summary

Introduction

Lung cancer is the leading cause of cancer mortality worldwide. It accounts for 22% of total cancer mortalities with only a 7% 5‐year survival expectancy in the United Kingdom [1]. Non‐small cell lung cancer (NSCLC) accounts for ~80% of all diagnosed cases of lung cancer [2]. Chemotherapy plays an important role in the treatment of NSCLC. Anticancer drugs exert their therapeutic action mainly by inducing tumor cell apoptosis.

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