PERK/eIF-2α/CHOP Pathway Dependent ROS Generation Mediates Butein-induced Non-small-cell Lung Cancer Apoptosis and G2/M Phase Arrest

International Journal of Biological Sciences
Shouyin DiXiaolong Yan

Abstract

Butein, a member of the chalcone family, is a potent anticarcinogen against multiple cancers, but its specific anti-NSCLC mechanism remains unknown. The present study examined the effects of butein treatment on NSCLC cell lines and NSCLC xenografts. Butein markedly decreased NSCLC cell viability; inhibited cell adhesion, migration, invasion, and colony forming ability; and induced cell apoptosis and G2/M phase arrest in NSCLC cells. Moreover, butein significantly inhibited PC-9 xenograft growth. Both in vivo and in vitro studies verified that butein exerted anti-NSCLC effect through activating endoplasmic reticulum (ER) stress-dependent reactive oxygen species (ROS) generation. These pro-apoptotic effects were reversed by the use of 4- phenylbutyric acid (4-PBA), CHOP siRNA, N-acetyl-L-cysteine (NAC) and Z-VAD-FMK (z-VAD) in vitro. Moreover, inhibition of ER stress markedly reduced ROS generation. In addition, in vivo studies further confirmed that inhibition of ER stress or oxidative stress partially abolished the butein-induced inhibition of tumor growth. Therefore, butein is a potential therapeutic agent for NSCLC, and its anticarcinogenic action might be mediated by ER stress-dependent ROS generation and the apoptosis pathway.

Citations

Dec 4, 2020·Journal of Hematology & Oncology·Tianming ZhaoHui Zeng
Apr 25, 2021·Biochemical and Biophysical Research Communications·Yunpeng LeiGuoqing Lv
Jun 3, 2021·Cancers·Radka MichalkovaJan Mojzis
Jul 3, 2021·Biomolecules·Yang OuyangQi Wu
Jul 17, 2021·Biochemical and Biophysical Research Communications·Zahra Habibi-KelishomiAlireza Nikoofar
Dec 7, 2021·Natural Product Research·Paloma Silva de SouzaMichelle Frazão Muzitano

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Methods Mentioned

BETA
confocal microscopy
RNA-seq
xenograft
transfection
xenografts

Software Mentioned

Multiple experiment viewer
SPSS
Image Pro Plus

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