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Propolis and related polyphenolic compounds increase cytotoxicity of irinotecan to tumor cells and protect normal cells

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 (HEp2 and resistant VK-2) in vitro were investigated. Test components (100 mg kg-1) and/or irinotecan (50 mg kg-1) were given intraperitoneally prior or after the intraperitonel injection of EAT (2 x106) cells. Antitumor, genotoxic, hemostimulative and immunomodulatory effects were investigated. We found complete abrogation of tumor growth and survival of 50% animals treated preventively with irinotecan combined with WSDP and EEP. When given therapeutically combined treatment with test components and irinotecan increased life span in all tested groups. Total number of cells present in the peritoneal cavity was significantly (p<0.05) reduced in EAT-bearing mice treated preventively or curatively with test components combined with irinotecan, indicating synergistic cytotoxic effects. Results suggested that propolis and flavonoids can modulate P-gp function and that they could be used in some combination as safe and potent MDR reversing agents in clinical chemotherapy. To conclude, combined treatment may be beneficial in maximizing antitumor activity and minimizing post-chemotherapeutic reactions on leukocytes, hepatocytes and kidney cells.

Ehrlich ascites tumor; propolis; flavonoids; irinotecan; tumor growth; P-gp function; comet assay; hematological and biocemical parameters

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