Mechanistic insights into anti-cancer properties of oligomeric proanthocyanidins from grape seeds in colorectal cancer

Although the anti-cancer properties of Oligomeric Proanthocyanidins (OPCs) from grape seeds has been well recognized, the molecular mechanisms by which they exert anti-cancer effects are poorly understood. In this study, through comprehensive RNA-sequencing based gene-expression profiling in multiple colorectal cancer cell lines, we for the first time illuminate the genome-wide effects of OPCs from grape seeds in colorectal cancer. Our data revealed that OPCs affects several key cancer-associated genes. In particular, genes involved in cell cycle and DNA replication were most significantly and consistently altered by OPCs across multiple cell lines. Intriguingly, our in vivo experiments showed that OPCs was significantly more potent at decreasing xenograft tumor growth compared to the unfractionated grape seed extract (GSE) that includes the larger polymers of proanthocyanidins. These findings were further confirmed in colorectal cancer patient-derived organoids, wherein OPCs more potently inhibited the formation of organoids compared to GSE. Further, we validated alteration of cell cycle and DNA replication associated genes in cancer cell lines, mice xenografts as well as patient-derived organoids. Overall, this study provides an unbiased and comprehensive look at the mechanisms by which OPCs exerts anti-cancer properties in colorectal cancer. 30 total samples consisting of 6 samples for each of 5 cell lines; From each group of 6 samples 2 were treated with DMSO (control), 2 were treated with grape seed extract (GSE), and 2 were treated with oligomeric proanthocyanidins (OPCs)