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Benefits of use of propolis and related flavonoids against the toxicity of chemotherapeutic agents

Standard cancer therapies commonly require multiple agents. However, use of multiple agents contributes to increased toxicity resulting in poor treatment outcome. Thus, combined chemotherapy must be optimized to increase tumor response and at the same time lower its toxicity. Antioxidants have been shown to enhance the effect of certain chemotherapeutic agents on tumor cells in vitro and in vivo. However, this effect differs depending upon the type of tumor and the drugs. The objective of this study was to see whether pretreatment with antioxidant mixture could enhance the cytotoxic and apoptotic effect of commonly used chemotherapeutic agents, irinotecan, cisplatin, doxorubicin and epirubicin for the treatment of Echrlich ascites tumor or of mammary carcinoma in mice. Chemotherapeutic agents are known to induce nuclear factor KB (NF- B) activity in tumor cells, resulting in lower cell killing and drug resistance. Collectively, our studies and those by others showed that different polyphenolic/flavonoid components separated from propolis as well as propolis alone could „ sensitize“ cancer cells to chemotherapeutic agents, likely by blocking NF- B activation induced by chemotherapeutic agents both in vitro and in vivo. These results provide experimental evidence showing that novel therapeutic strategies for human cancer could be developed to achieve better treatment outcome by introducing flavonoids in the therapeutic regimen. Positive outcome of combined treatment with propolis and chemotherapeutics was expressed by the influence of these treatments on reduced cytotoxicity to peripheral blood leukocytes, liver and kidney cells.Therefore, polyphenolic/flavonoid components could be potentially useful in combination with chemotherapeutic agents for the treatment of different types of human cancer.

Propolis, Flavonoids, Chemoterapeutics, Immunomodulation, Genotoxicity

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