Preclinical evidences of antitumoral properties of a yerba mate extract on breast and colon cancer models

GARCIA-LAZARO RS; LAMDAN H; LORENZO N; CALIGIURI L; BERENGENO AL; ORTEGA HH; ALONSO DF; FARINA HG

Filadelfia

Congreso; American Association for Cancer Research Annual meeting; 2020

American Association for Cancer Research

Yerba Mate (Ilex Paraguariensis) belongs to the Aquifoliaceae family and is a native plant of South America. This plant are enriched in bioactive compounds with biological activities. This study investigated the antitumor activity of Yerba Mate extract (YM) using in vitro and in vivo colon and breast cancer models. YM was generated by aqueous extraction and standardized to total phenolics content, antioxidant activity and Chlorogenic acid content. The HPLC analysis of the YM allowed us to quantify the main polyphenols: Chlorogenic acid (66.3 ± 0.05 mg/g dry sample), Rutin (6.783 ± 0.05 mg/g dry sample), Gallic acid (6.665 ± 0.321 mg/g dry sample), Caffeic acid (0.533 ± 0.04 mg/g dry sample) and Quercetin (0.229 ± 0.02 mg/g dry sample). To investigate the antitumoral activity of YM, we first evaluated its effect on cell proliferation of colon (CT26 and COLO205) and breast (MDA-MB 231, MCF7, F3II and 4T1) cancer cell lines. YM reduced tumor cell viability and induced apoptosis. In addition, YM showed negative modulatory effect on cell adhesion and migration of tumor cells and reduced their invasiveness capacity. The use of herbal products requires previous toxicity studies to identify the dose ranges that are safe for subsequent studies. Acute toxicity was evaluated in rats and chronic toxicity test was conducted in rabbits. Animals exposed showed no statistical changes in weight gain. Clinical examination and macroscopic analysis did not show any changes that indicate toxicity. We found a YM LD50 value above 5000 mg/kg. The effect of YM on tumor progression was also studied in vivo using different syngeneic tumor models. Animals received YM by oral administration in a dose of 1.6 g/kg/day before and after tumor cell inoculation. Orthotopic and heterotopic breast cancer models in BALB/c mice was performed. In the heterotopic F3II model the treatment with YM significantly reduced tumor volumes when compared with control group. In addition, the consumption of YM significantly increased the survival of animals in both models. We also studied the inhibition of spontaneous metastatic activity by YM. Diet with YM resulted in a reduced number of lung metastases compared to control in both models. On the other hand, in the heterothopic colorectal cancer model we observed that oral administration of YM reduced angiogenesis, delayed tumor onset and showed a reduction of tumor volume. The effects of the combination of YM extract with 5-fluorouracil (5-FU) was also evaluated in mice. The results suggest that this combination increased susceptibility of the colon cancer cells to the cytotoxicity of 5-Fu. In conclusion, our findings suggest that YM may be a promising agent for the treatment of breast and colon cancer in chemoprevention schemes or in combinatory schedules with standard-of-care therapeutics.