Dehydrodiisoeugenol inhibits colorectal cancer growth by endoplasmic reticulum stress-induced autophagic pathways

Journal of Experimental & Clinical Cancer Research

Research

Yi Wang¹  Xiaowen Wang²  Kui Zhang²  Haoyan Ji²  Chongyang Li²  Ruochen Liu²  Guangzhao Pan²  Longfei Deng²  Xin Hu²  Hongjuan Cui³  Changhong Li³  Liqun Yang³ 

[1] Affiliated Hospital of Southwest University (the Ninth People’s Hospital of Chongqing), 400716, Chongqing, China;State Key Laboratory of Silkworm Genome Biology, College of Sericulture, Textile and Biomass sciences, Southwest University, #2, Tiansheng Rd., Beibei District, 400716, Chongqing, China;Cancer Centre, Medical Research Institute, Southwest University, 400716, Chongqing, China;State Key Laboratory of Silkworm Genome Biology, College of Sericulture, Textile and Biomass sciences, Southwest University, #2, Tiansheng Rd., Beibei District, 400716, Chongqing, China;Cancer Centre, Medical Research Institute, Southwest University, 400716, Chongqing, China;Affiliated Hospital of Southwest University (the Ninth People’s Hospital of Chongqing), 400716, Chongqing, China;

关键词: Colorectal cancer;    Dehydrodiisoeugenol (DEH);    Autophagy inhibition;    Endoplasmic reticulum (ER) stress;    Anticancer agent;   

DOI  :  10.1186/s13046-021-01915-9

 received in 2020-12-03, accepted in 2021-03-16,  发布年份 2021

来源: Springer

【 摘 要 】

BackgroundDehydrodiisoeugenol (DEH), a novel lignan component extracted from nutmeg, which is the seed of Myristica fragrans Houtt, displays noticeable anti-inflammatory and anti-allergic effects in digestive system diseases. However, the mechanism of its anticancer activity in gastrointestinal cancer remains to be investigated.MethodsIn this study, the anticancer effect of DEH on human colorectal cancer and its underlying mechanism were evaluated. Assays including MTT, EdU, Plate clone formation, Soft agar, Flow cytometry, Electron microscopy, Immunofluorescence and Western blotting were used in vitro. The CDX and PDX tumor xenograft models were used in vivo.ResultsOur findings indicated that treatment with DEH arrested the cell cycle of colorectal cancer cells at the G1/S phase, leading to significant inhibition in cell growth. Moreover, DEH induced strong cellular autophagy, which could be inhibited through autophagic inhibitors, with a rction in the DEH-induced inhibition of cell growth in colorectal cancer cells. Further analysis indicated that DEH also induced endoplasmic reticulum (ER) stress and subsequently stimulated autophagy through the activation of PERK/eIF2α and IRE1α/XBP-1 s/CHOP pathways. Knockdown of PERK or IRE1α significantly decreased DEH-induced autophagy and retrieved cell viability in cells treated with DEH. Furthermore, DEH also exhibited significant anticancer activities in the CDX- and PDX-models.ConclusionsCollectively, our studies strongly suggest that DEH might be a potential anticancer agent against colorectal cancer by activating ER stress-induced inhibition of autophagy.

【 授权许可】

CC BY   
© The Author(s) 2021. corrected publication 2023

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