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Biomed Pharmacother. 2017 Sep;93:490-497. doi: 10.1016/j.biopha.2017.06.073. Epub 2017 Jun 30.

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

Author information

1
Key Laboratory of New Drug Delivery Systems of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu Nanjing, 210028, PR China; School of Pharmacy, Anhui University of Chinese Medicine, Anhui Hefei 230038, PR China.
2
Key Laboratory of New Drug Delivery Systems of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu Nanjing, 210028, PR China; Third School of Clinical Medical of Nanjing University of Chinese Medicine, Jiangsu Nanjing 210028, PR China.
3
Key Laboratory of New Drug Delivery Systems of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu Nanjing, 210028, PR China.
4
The Affiliated Jiangyin Hospital of Southeast University Medical Collage, Jiangyin 214400, Jiangsu, PR China.
5
Key Laboratory of New Drug Delivery Systems of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu Nanjing, 210028, PR China; Third School of Clinical Medical of Nanjing University of Chinese Medicine, Jiangsu Nanjing 210028, PR China. Electronic address: jxiaobin2005@hotmail.com.
6
Key Laboratory of New Drug Delivery Systems of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu Nanjing, 210028, PR China; Third School of Clinical Medical of Nanjing University of Chinese Medicine, Jiangsu Nanjing 210028, PR China. Electronic address: wenmoxiushi@163.com.

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 cell apoptosis 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 and down-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.

KEYWORDS:

Apoptosis; Endoplasmic reticulum stress; Non-small-cell lung cancer; β-elemene

PMID:
28672279
DOI:
10.1016/j.biopha.2017.06.073
[Indexed for MEDLINE]

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