Induction of Apoptosis and Cell-Cycle Arrest in Human Colon-Cancer Cells by Whole-Grain Alkylresorcinols via Activation of the p53 Pathway
Fu J, Soroka DN, Zhu Y, Sang S
Journal of agricultural and food chemistry · 22 citations
Review labels
Neutral facts our review recorded about how this study was done. They describe method, never whether we like the result.
How it was studied
- Design
- In vitro/mechanistic study (classified by our AI screen)
- Studied in
- Cells or lab samples
- Main outcome
- Mechanisms only
Who paid for it
- Funding
- Independent funding
- Government
- National Institute of Food and Agriculture
- Grants
- National Institute of Food and Agriculture (2012-38821-20012)
Based on 1 listed funder(s).
Publication
- Published
- 2018-10-24 · J Agric Food Chem · vol. 66 · issue 45 · pp. 11935–11942
- Publisher
- American Chemical Society
- Cited
- 33 citations · more than 82% of similar papers · 1.2× the field average
- References
- 29 works
- Access
- Paywalled
- Research areas
- Cancer-related Molecular Pathways · Cancer, Lipids, and Metabolism · Cancer, Hypoxia, and Metabolism
- Keywords
- Apoptosis, Downregulation and upregulation, Colorectal cancer, Cancer research, Cell cycle, Cell cycle checkpoint, Cancer, Programmed cell death, Mdm2, Cell biology, Cancer cell, Chemistry, Puma, Signal transduction, Biology, Biochemistry, Genetics
- MeSH
- cell line, tumor, mitochondria, humans, colonic neoplasms, resorcinols, plant extracts, antineoplastic agents, apoptosis, tumor suppressor protein p53, cyclin-dependent kinase inhibitor p21, proto-oncogene proteins c-mdm2, proteolysis, cell cycle checkpoints, whole grains
4 authors
From US, CN
- Junsheng FuNorth Carolina Agricultural and Technical State University; Fujian Agriculture and Forestry University
- Dominique N. SorokaNorth Carolina Agricultural and Technical State University
- Yingdong ZhuNorth Carolina Agricultural and Technical State University
- Shengmin Sang · correspondingUniversity of North Carolina at Chapel Hill; North Carolina Agricultural and Technical State University
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.
Abstract via Europe PMC. Copyright remains with the authors or publisher.
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