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Antitumor and anticytopenic effect of propolis and related polyphenolic compounds in combination with chemotherapeutic irinotecan

Effects of ethanolic extract of propolis (EEP), water-soluble derivate of propolis (WSDP), quercetin and naringin combined with anticancer drug irinotecan on the Ehrlich ascites tumor (EAT) in Swiss albino mice and cell lines (human larynx carcinoma HEp2 and resistant VK-2) in vitro were investigated. Test components (100 mg kg-1) and/or irinotecan (50 mgkg-1) were given intraperitoneally prior or after the intraperitoneal injection of EAT (2 x106) cells. Antitumor, genotoxic, hemostimulative and immunomodulatory effects were investigated. When given therapeutically combined treatment with test components and irinotecan increased life span in all tested groups. Propolis (100  g ml-1) and flavonoids (100  M) decreased function of P-gp of HEp2 cells, while this effect in resistant VK-2 cells was slightly increased. All test compounds combined with irinotecan in concentration of 1 and 10 μ M decreased activity of P-gp pumps. Test compounds combined with vincristine 0.05 μ M showed enhanced P-gp activity ; while naringin and quercetin combined with vincristine 0.5  M decreased activity of P-gp. These results suggested that propolis and flavonoids modulate P-gp function and that they could be used as MDR reversing agents in clinical chemotherapy. The results of present study suggest that clinical trials using a WSDP, EEP, quercetin and naringin combined with cytostatic drugs may be beneficial in maximizing antitumor activity and minimizing post-chemotherapeutic reactions.

Propolis; Flavonoids; Irinotecan; Tumor resistance; Pg-p activity

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