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J Agric Food Chem. 2018 Nov 14;66(45):11935-11942. doi: 10.1021/acs.jafc.8b04442. Epub 2018 Oct 31.

Induction of Apoptosis and Cell-Cycle Arrest in Human Colon-Cancer Cells by Whole-Grain Alkylresorcinols via Activation of the p53 Pathway.

Author information

1
College of Life Sciences , Fujian Agriculture and Forestry University , Number 15 Shangxiadian Road , Fuzhou City , Fujian Province 350002 , PR China.
2
Laboratory for Functional Foods and Human Health, Center for Excellence in Post-Harvest Technologies , North Carolina Agricultural and Technical State University , North Carolina Research Campus, 500 Laureate Way , Kannapolis , North Carolina 28081 , United States.
3
Lineberger Comprehensive Cancer Center , The University of North Carolina at Chapel Hill , 450 West Drive, CB# 7295 , Chapel Hill , North Carolina 27599 , United States.

Abstract

Colon cancer, one of the leading causes of cancer-associated deaths, is the target of choice for nutrition-based-prevention approaches because of the direct and early contact between the active compounds and the cancerous tissues. We previously reported alkylresorcinols (ARs) as the major active components in wheat bran against human colon cancer. Here, we further investigate the anticancer mechanisms of action of ARs. Our mechanistic studies indicated that AR C15 and AR C17 exert their anticancer activities in colon-cancer cells by inducing apoptosis through PUMA upregulation and mitochondrial-pathway activation, inducing cell-cycle arrest through p21 upregulation, and inhibiting proteasome activity and Mdm2 expression. This cascade of distinct mechanisms was linked to the consequent activation and accumulation of p53. The results of treatment with p53 inhibitor further confirmed that the p53 pathway might play a very important role in AR-induced apoptosis in colon-cancer cells. Altogether these results show that AR C15 and AR C17 can specifically activate the mitochondrial pathway of apoptosis and cause cell-cycle arrest and that inhibition of p53 greatly reduces the activation of this pathway.

KEYWORDS:

alkylresorcinol; colon cancer; molecular mechanism; p53 pathway; whole grains

PMID:
30354111
DOI:
10.1021/acs.jafc.8b04442
[Indexed for MEDLINE]

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