Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Dehydrodiisoeugenol Inhibits Colorectal Cancer Growth by Endoplasmic Reticulum Stress Induced Autophagic Pathways

Version 1 : Received: 28 November 2020 / Approved: 1 December 2020 / Online: 1 December 2020 (14:57:00 CET)

How to cite: Li, C.; Kui, Z.; Guangzhao, P.; Haoyan, J.; Chongyang, L.; Xiaowen, W.; Yi, W.; Ruochen, L.; Longfei, D.; Cui, H.; Liqun, Y. Dehydrodiisoeugenol Inhibits Colorectal Cancer Growth by Endoplasmic Reticulum Stress Induced Autophagic Pathways. Preprints 2020, 2020120032 (doi: 10.20944/preprints202012.0032.v1). Li, C.; Kui, Z.; Guangzhao, P.; Haoyan, J.; Chongyang, L.; Xiaowen, W.; Yi, W.; Ruochen, L.; Longfei, D.; Cui, H.; Liqun, Y. Dehydrodiisoeugenol Inhibits Colorectal Cancer Growth by Endoplasmic Reticulum Stress Induced Autophagic Pathways. Preprints 2020, 2020120032 (doi: 10.20944/preprints202012.0032.v1).

Abstract

Dehydrodiisoeugenol (DEH), a novel lignan component extracted from the Nutmeg seeds, displays noticeable anti-inflammatory and anti-allergic effects in digestive system diseases. However, the mechanism of its anti-cancer activity in gastrointestinal cancer is still to be investigated. Here, the anti-cancer effect of DEH to human colorectal cancer and its underlying mechanism were evaluated. The DEH treatment arrests the cell cycle of colorectal cancer cells at G1/S phase, which leading to a significant cell growth inhibition. Moreover, it can induce strong cellular autophagy and the autophagy would be inhibited through autophagic inhibitors with reducing EDH-induced inhibition of cell growth in colorectal cancer cells. Further studies indicated that DEH can also induce endoplasmic reticulum (ER) stress, and could subsequently stimulating autophagy through activating PERK/eIF2α and IRE1α/XBP-1s/CHOP pathways. Knockdown of PERK or IRE1α can significantly decrease the DEH-induced autophagy and retrieve cell viability in cells treated with DEH. What’s more, DEH exhibits significant anti-cancer activities through CDX- and PDX-model as well. Taken together, our studies strongly suggest that DEH might be a potential anti-cancer agent against colorectal cancer via activating ER stress-induced autophagy inhibition.

Supplementary and Associated Material

https://www.gesa-info.de/: Using for data analysis.

Subject Areas

Colorectal cancer; Dehydrodiisoeugenol (DEH); Autophagy inhibition; Endoplasmic reticulum (ER) stress; anti-cancer agent

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