Emodin induces apoptosis of lung cancer cells through ER stress and the TRIB3/NF-κB pathway

Su,Jin; Yan,Yan; Qu,Jingkun; Xue,Xuewen; Liu,Zi; Cai,Hui

doi:10.3892/or.2017.5428

Emodin induces apoptosis of lung cancer cells through ER stress and the TRIB3/NF-κB pathway

Authors:
- Jin Su
- Yan Yan
- Jingkun Qu
- Xuewen Xue
- Zi Liu
- Hui Cai
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Affiliations: Department of Radiotherapy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China, The Second Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China, Department of Surgery, Xi'an Feng Cheng Hospital, Xi'an, Shaanxi, P.R. China, Department of Vascular Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China
Published online on: February 7, 2017 https://doi.org/10.3892/or.2017.5428
Pages: 1565-1572

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Abstract

Emodin is a phytochemical with potent anticancer activities against various human malignant cancer types, including lung cancer; however, the molecular mechanisms underlying the effects of emodin remain unclear. In the present study, the A549 and H1299 human non-small lung cancer cell lines were treated with emodin and the induced molecular effects were investigated. Changes in cell viability were evaluated by MTT assay, Hoechst staining was used to indicate the apoptotic cells, and western blotting was utilized to assess endoplasmic reticulum (ER) stress and signaling changes. RNA interference was also employed to further examine the role of tribbles homolog 3 (TRIB3) in the emodin-induced apoptosis of lung cancer cells. Emodin was found to reduce the viability of lung cancer cells and induce apoptosis in a concentration-dependent manner. Emodin-induced apoptosis was impaired by inhibition of ER stress using 4-phenylbutyrate (4-PBA). ER stress and TRIB3/nuclear factor-κB signaling was activated in emodin-treated lung cancer cells. Emodin-induced apoptosis was reduced by TRIB3 knockdown in A549 cells, whereas ER stress was not reduced. In vivo assays verified the significance of these results, revealing that emodin inhibited lung cancer growth and that the inhibitory effects were reduced by inhibition of ER stress with 4-PBA. In conclusion, the results suggest that TRIB3 signaling is associated with emodin-induced ER stress-mediated apoptosis in lung cancer cells.

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