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Abstract Title:

β-elemene regulates endoplasmic reticulum stress to induce the apoptosis of NSCLC cells through PERK/IRE1α/ATF6 pathway.

Abstract Source:

Biomed Pharmacother. 2017 Sep ;93:490-497. Epub 2017 Jun 30. PMID: 28672279

Abstract Author(s):

Ying Liu, Zi-Yu Jiang, Yuan-Li Zhou, Hui-Hui Qiu, Gang Wang, Yi Luo, Jing-Bing Liu, Xiong-Wei Liu, Wei-Quan Bu, Jie Song, Li Cui, Xiao-Bin Jia, Liang Feng

Article Affiliation:

Ying Liu

Abstract:

Endoplasmic reticulum stress (ERs) has been regarded as an important cause for the pathogenesis of non-small-cell lung cancer (NSCLC).β-elemene is an active component in the essential oil extracted from a medicinal herb, Curcuma wenyujin, and has been reported to be effective against non-small-cell lung cancer (NSCLC). However, the potential effect and underlying mechanisms of β-elemene on regulating ERs to inhibit NSCLC are still unclear. In the present study, A549 cells and Lewis tumor-bearing C57BL/6J mice were established to evaluate this effect. Visualsonics Vevo 2100 Small Animal Dedicated High-frequency Color Ultrasound was performed to observe tumor volume in vivo. 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) was used to evaluate cell vitality of A549 cells. Furthermore, western blotting (WB), immunohistochemistry (IHC) and quantitative reverse transcription polymerase chain reaction (q-PCR) were applied to detect the ERs-related proteins. Flow cytometry was also applied to detect cellapoptosis and assay kit for reactive oxygen species (ROS) generation. Our results showed that β-elemene inhibited lung cancer tumor growth and cell vitality in a dose- and time-dependent manner. Not only that, β-elemene could up-regulate ERs-related proteins like PERK, IRE1α, ATF6, ATF4, CHOP anddown-regulate the Bcl-2 expression. More importantly, ERs inhibitor 4-PBA, IRE1α inhibitor STF-083010, ATF6 inhibitor Anti-ATF6 and PERK inhibitor GSK2656157 can all reduce the amplitude of protein expression changes and apoptosis rates, then weaken the anti-tumor effect of β-elemene. Therefore,the present in vivo and in vitro study revealed that the anti-NSCLC effect of β-elemene is closely related to the activation of ERs through PERK/IRE1α/ATF6 pathway, and this might be beneficial for clinical therapy of NSCLC.

Study Type : In Vitro Study

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