Cancer stem cells, the “seeds” of recurring cancer, resist chemotherapy. They essentially hide in the body, remerging later – sometimes years following treatment. When this happens, the new cancer is even more resistant to treatment.

Researchers at Baylor found that French grape seed extract (VX1) stopped the regeneration of cancer stem cells by blocking a specific pathway in the body, abbreviated as “HIPPO-Yap.” It actually prevented the ability of tumor cells to grow and spread, and eventually, this kills them altogether. This is an effect not seen with conventional drugs, so these results show the potential for OPCs from grape seed to do something completely unique. In this case, the viability of cancer cells exposed to the extract decreased by 70 percent. Further study using an animal model showed that the VX1 extract suppressed tumor growth by up to 90 percent.

This study shows that the frontiers of natural cancer fighting are still being crossed and that the potential for the right kind of grape seed extract – one that is tannin free and specifically standardizes for OPCs – is massive. According to the researchers, a human equivalent dose could be a small addition to a daily regimen – only about 300 mg to 600 mg per day.

Abstract:

Toden S, Ravindranathan P, Gu J, Cardenas J, Yuchang M, Goel A. Oligomeric proanthocyanidins (OPCs) target cancer stem-like cells and suppress tumor organoid formation in colorectal cancer. Sci Rep. 2018 Feb 20;8(1):3335.

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.