Bioactive Compounds of Rheum ribes L. and its Anticancerogenic Effect via Induction of Apoptosis and miR-200 Family Expression in Human Colorectal Cancer Cells

Rheum ribes L. is a widespread plant species in the eastern part of our country and is consumed as a vegateble by the folk people. In our study, we investigated whether R. ribes has anti-cancerogenic effect on colorectal cancer cell lines. Six different extracts were obtained from R. ribes. Total phenolic, flavonoid contents, antioxidant activities, and cytotoxic effects of all extracts on colorectal cancer cells were determined. Differences in expression levels of the miR-200 family and target genes were assessed by real-time qPCR in cells. Antiproliferative effect was determined by TUNEL, Annexin V, cell cycle, invasion analysis; and levels of BCL-2, ZEB1, GATA4 and FAS/CD95 proteins were determined by ELISA. According to the results of miRNA expression analysis, the only dose group with a significant increase (p < 0,05) in the expression level of all of miRNAs in both cell lines was RM (Root methanol) extract alone. Our results showed that, RM caused a significant increase in the expressions of miR-200a/b/c and miR-141, and it suppressed BCL-2, ZEB1, GATA4 expressions, with this way. Thus, it has been suggested that the treatment of RM alone, or combined treatment of RM with 5-FU result in a better response than cancer cells treated with 5-FU alone.