Journal
SCIENTIFIC REPORTS
Volume 8, Issue -, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41598-018-21478-8
Keywords
-
Categories
Funding
- National Cancer Institute, National Institute of Health [CA72851, CA181572, CA184792, CA187956, CA202797]
- Cancer Prevention Research Institute of Texas (CPRIT) [RP140784]
- Baylor Sammons Cancer Center and Foundation
- Baylor Research Institute
Ask authors/readers for more resources
Proanthocyanidins are a heterogeneous group of flavan-3-ol or flavan-3,4-diol oligomers present in various fruits and vegetables. In particular, the smaller oligomeric subset of proanthocyanidins, termed the oligomeric proanthocyanidins (OPCs) appear to have potent anti-tumorigenic properties, but the underlying mechanisms for their effectiveness remain unclear. Herein, we utilized a series of in vitro, in vivo and patient-derived organoid approaches to systematically investigate the chemoprotective role of OPCs in colorectal cancer. OPCs exerted anti-tumorigenic effects through inhibition of cellular proliferation, and induced apoptosis and cell cycle arrest. Intriguingly, OPCs suppressed spheroid derived cancer stem-like cell formation and decreased the expression of intestinal cancer stem cell markers including LGR5, CD44 and CD133. Mechanistically, RNA-sequencing results confirmed that OPCs prominently interfered with developmental and self-renewal pathways and identified several self-renewal associated oncogenes targeted by OPCs. Furthermore, OPCs inhibited Hippo pathway through downregulation of its key transcriptional regulators, YAP and TAZ. Finally, we confirmed anti-tumorigenic effects of OPCs using multiple xenograft experiments and recapitulated its protective effects using patient-derived colorectal tumor organoids. Collectively, we have comprehensively assessed anti-tumorigenic properties of OPCs and our data throws light on previously unrecognized chemopreventive mechanisms of OPCs highlighting its therapeutic potential.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available