Decursin Induces G1 Cell Cycle Arrest and Apoptosis through Reactive Oxygen Species-Mediated Endoplasmic Reticulum Stress in Human Colorectal Cancer Cells in In Vitro and Xenograft Models

被引:2
作者
Kim, Danbee [1 ]
Go, Seok-Ho [1 ]
Song, Yeeun [1 ]
Lee, Dong-Keon [1 ]
Park, Jeong-Ran [1 ]
机构
[1] Scripps Korea Antibody Inst, Div Res Ctr, Chunchon 24341, South Korea
关键词
decursin; apoptosis; endoplasmic reticulum stress; reactive oxygen species; colorectal cancer; GASTRIC-CANCER; ER STRESS; GROWTH; AUTOPHAGY;
D O I
10.3390/ijms25189939
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Decursin, a coumarin isolated from Angelica gigas Nakai, possesses anti-inflammatory and anti-cancer properties. However, the molecular mechanisms underlying its anti-cancer effects against human colorectal cancer (CRC) are unclear. Therefore, this study aimed to evaluate the biological activities of decursin in CRC in vitro and in vivo and to determine its underlying mechanism of action. Decursin exhibited anti-tumor activity in vitro, accompanied by an increase in G1 cell cycle arrest and apoptosis in HCT-116 and HCT-8 CRC cells. Decursin also induced the production of reactive oxygen species (ROS), thereby activating the endoplasmic reticulum (ER) stress apoptotic pathway in CRC cells. Furthermore, the role of ROS in decursin-induced apoptosis was investigated using the antioxidant N-acetyl-L-cysteine. Inhibiting ROS production reversed decursin-induced ER stress. Moreover, decursin significantly suppressed tumor growth in a subcutaneous xenograft mouse model of HCT-116 and HCT-8 CRC cells without causing host toxicity. Decursin also decreased cell proliferation, as documented by Ki-67, and partly increased cleaved caspase 3 expression in tumor tissues by activating ER stress apoptotic pathways. These findings suggest that decursin induces cell cycle arrest and apoptosis in human CRC cells via ROS-mediated ER stress, suggesting that decursin could be a therapeutic agent for CRC.
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页数:17
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