Anti-proliferative activity of yerba mate (Ilex paraguariensis) aqueous extracts on human colorectal cancer cell lines

Background: Yerba mate, a popular, tea-like beverage prepared from the dried leaves of Ilex paraguariensis, is widely consumed, and has several reported health benefits. Compared with other herbal teas, the effect of yerba mate on human cells in the context of cancer has not been extensively studied. The method of extraction of bioactive compounds from the yerba mate leaves plays an important role in its effect on cancer cells. Methods: In this study we assessed the viability, anti-proliferative, and apoptotic effect of the aqueous yerba mate extract, prepared using the same conditions employed for consumption, on different human colorectal cancer cell lines (Caco-2, HT-29, and HCT116) and on the non-tumorigenic human colon epithelial cell line (NCM460).Results: Cytotoxicity of aqueous yerba mate extract was studied and a dose-dependent decrease in viability was observed in all the tested cell lines. At 24 hrs., viability decreased to 19.7% with Caco-2 cells, 2.7% with HCT116, and 8.4% with HT-29 cells at a concentration of 4.8 mg/mL of yerba mate extract. The effect was less prominent on the NCM460 cell line where the viability of cells at the same concentration was 65.2%. Yerba mate extract also showed concentration-dependent anti-proliferative effects as determined by the WST-1 proliferation kit. IC50 values ranged between 0.22-0.69 mg/mL at 24 hr for cell lines tested. To study whether cell death was due to apoptosis, Caco-2 cells were stained with Annexin V-FITC assay and an increase in the percentage of late apoptotic Caco-2 cells was observed with yerba mate extract at 0.6-4.8 mg/mL. Cell cycle analysis using DNA content by flow cytometry showed an increase in the percentage of Caco-2 cells in the subG0/G1 phase and the G0/G1 phase after treatment with 2.4 mg/mL extract. Collectively, our data suggest that yerba mate aqueous extract exhibits an anti-proliferative effect on tested cell lines by inducing apoptosis.  Conclusions: Yerba mate aqueous extract exhibits a strong anti-proliferative activity against adenocarcinoma cell lines studied and constitutes a promising functional food adjuvant to anti-cancer therapy. Further work is needed to identify active components and mechanisms of action. Keywords: Aqueous extract, yerba mate, anti-proliferative activity, adenocarcinoma cell lines