Crassolide Induces G2/M Cell Cycle Arrest, Apoptosis, and Autophagy in Human Lung Cancer Cells via ROS-Mediated ER Stress Pathways

CNU IR > Pharmacy and Science > Dept. of Cosmetic Science and institute of cosmetic science > Periodical Articles > Item 310902800/34604

Please use this identifier to cite or link to this item: https://ir.cnu.edu.tw/handle/310902800/34604

Title:	Crassolide Induces G2/M Cell Cycle Arrest, Apoptosis, and Autophagy in Human Lung Cancer Cells via ROS-Mediated ER Stress Pathways
Authors:	Lai, Kuan-Ming Wang, Jou-Hsuan Lin, Shih-Chao Wen, Ya Wu, Chao-Liang Su, Jui-Hsin Chen, Chien-Chin Lin, Chi-Chien
Contributors:	National Chung Hsing University Changhua Christian Hospital National Chung Hsing University National Taiwan Ocean University Karolinska Institutet National Museum of Marine Biology & Aquarium Department of Cosmetic Science, Chia Nan University of Pharmacy & Science China Medical University Taiwan China Medical University Hospital - Taiwan Taichung Veterans General Hospital Kaohsiung Medical University Asia University Taiwan
Keywords:	endoplasmic-reticulum stress cytotoxic cembranolides soft corals mitochondria checkpoints cdc25c death
Date:	2022
Issue Date:	2023-12-11 14:00:21 (UTC+8)
Publisher:	MDPI
Abstract:	Crassolide, a cembranoid diterpene extracted from the soft coral Lobophytum crissum, has been proven to possess antioxidant and immunomodulatory properties. In the present study, we assessed the anticancer effects of crassolide on human H460 non-small-cell lung cancer (NSCLC) cells. We found that crassolide exerted cytotoxic effects on H460 cancer cells in vitro, inducing G2/M phase arrest and apoptosis. In addition, in H460 cells exposed to crassolide, the expression of the autophagy-related proteins LC3-II and beclin was increased, while the expression of p62 was decreased. Moreover, inhibiting autophagy with chloroquine (CQ) suppressed the crassolide-induced G2/M arrest and apoptosis of H460 cells. Moreover, we also found that crassolide induced endoplasmic reticulum (ER) stress in lung cancer cells by increasing the expression of ER stress marker proteins and that the crassolide-induced G2/M arrest, apoptosis, and autophagy were markedly attenuated by the ER stress inhibitor 4-phenylbutyric acid (4-PBA). Furthermore, we found that crassolide promoted reactive oxygen species (ROS) production by H460 cells and that the ROS inhibitor N-acetylcysteine (NAC) decreased the crassolide-induced ER stress, G2/M arrest, apoptosis, and autophagy. In conclusion, our findings show that crassolide inhibits NSCLC cell malignant biological behaviors for the first time, suggesting that this effect may be mechanistically achieved by inducing G2/M arrest, apoptosis, and autophagy through ROS accumulation, which activates the ER stress pathway. As a result of our findings, we now have a better understanding of the molecular mechanism underlying the anticancer effect of crassolide, and we believe crassolide might be a candidate for targeted cancer therapy.
Relation:	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v.23, n.10, 5624
Appears in Collections:	[Dept. of Cosmetic Science and institute of cosmetic science] Periodical Articles

Files in This Item:

File	Description	Size	Format
ijms23105624.pdf		13327Kb	Adobe PDF	123	View/Open
index.html		0Kb	HTML	160	View/Open

Loading...