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Background Blueberries are among the fruits with the highest antioxidant activity and have been recognized by their health promoting properties. Aim In vitro study of the anti-proliferative effects of a blueberry extract on a panel of cancer cells from different origin. Materials and methods A blueberry extract was produced using ethanol as extracting solvent. The anti-proliferative activity of the extract was evaluated against seven tumor cell lines. The properties of blueberry extract to decrease cell adhesion and migration were also investigated. Results Blueberry extract showed a dose-dependent inhibitory effect on cell proliferation for all cell lines. Non-cytotoxic concentrations of the extract decreased cell adhesion in five of seven cell lines studied and inhibited the migration of MDA-MB-231 and PC-3 tumor cells. Conclusion This work provides additional evidence regarding the ability of blueberry extract to inhibit the growth and decrease cell adhesion and migration of different cancer cell lines in vitro.

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. Citation Format: Rocío S. García Lázaro, Humberto Lamdan, Norailys Lorenzo Perez, Lorena G. Caligiuri, Andrea L. Berengeno, Hugo H. Ortega, Daniel F. Alonso, Hernan G. Farina. Preclinical evidences of antitumoral properties of a Yerba mate extract on breast and colon cancer models [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3455.

Following the clinical success of Bevacizumab, a humanized monoclonal antibody that blocks the interaction between vascular endothelial growth factor (VEGF) and its receptors, the search for new neutralizing antibodies targeting this molecule has continued until now. We used a human VEGF variant containing three mutations in the region recognized by Bevacizumab to direct antibody selection towards recognition of other epitopes. A total of seven phage-displayed antibody fragments with diverse binding properties in terms of inter-species cross-reactivity and sensitivity to chemical modifications of the antigen were obtained from a human phage display library. All of them were able to recognize not only the selector mutated antigen, but also native VEGF. One of these phage-displayed antibody fragments, denominated 2H1, was shown to compete with the VEGF receptor 2 for VEGF binding. Purified soluble 2H1 inhibited in a dose dependent manner the ligand-receptor interaction and abolished VEGF-dependent proliferation of human umbilical vein endothelial cells. Our epitope disturbing strategy based on a triple mutant target antigen was successful to focus selection on epitopes different from a known one. Similar approaches could be used to direct phage isolation towards the desired specificity in other antigenic systems.