Antitumor, hematostimulative and radioprotective action of water-soluble derivative of propolis (WSDP).
Several studies suggest that dietary supplementation with antioxidant can influence the response to chemotherapy as well as the development of adverse side effects caused by treatment with chemotherapeutic agents. Using CBA mouse model, we investigated a clinically potential use of a water-soluble derivative of propolis (WSDP) in the treatment of various cytopenias induced by radiation and/or chemotherapy. Also, the antimetastatic efficiency of WSDP given intraperitoneally alone or in combination with chemotherapeutic agents and their effects on the blood leukocytes count as well as on hematopoiesis were studied. Tumor was a transplantable mammary carcinoma (MCa) of CBA mouse. Metastases in the lung were generated by injecting viable tumor cells intravenously (iv). WSDP (50 or 150 mg/kg) exerted a significant antimetastatic effect (P < 0.001) when given either before or after tumor cell inoculation. In combined treatment WSDP and Epirubicin profoundly inhibited metastasis formation; this synergistic effect is maximal when Epirubicin and WSDP were administrated after tumor cell inoculation. Positive outcome of combined treatment with WSDP and Epirubicin was also found regarding the number of red and white blood cells in peripheral blood while in mice treated with Epirubicin alone the significant drop in all hematological parameters was noticed on day 13 after tumor cell inoculation. Furthermore, when WSDP (50 mg/kg) was given perorally (po) for 20 consecutive days an increased number of exogenous CFUs was found in treated mice. WSDP given either for 20 or 40 days increased cellularity of hematopoietic tissue and the number of leucocytes in peripheral blood; prolonged treatment with WSDP also elevated myeloid and megakaryocytic types of CFUs. To conclude, these findings indicate that the combination of WSDP with chemotherapeutics could increase the antimetastatic potential of chemotherapeutic agents; these findings suggest the benefits of potential clinical trials using WSDP combined with chemotherapeutic agents in order to maximize their antitumor activity and minimize postchemotherapeutic or radiotherapeutic deteriorated reactions.
Orsolić
Nada
N
Department of Animal Physiology, Faculty of Science, University of Zagreb, Rooseveltov trg 6, Croatia. norsolic@yahoo.com
Basić
Ivan
I
D000284:Administration, Oral; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D001772:Blood Cell Count; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005720:Gamma Rays; D006410:Hematopoiesis / Q000187:drug effects* / Q000528:radiation effects; D007274:Injections, Intraperitoneal; D007970:Leukopenia / Q000209:etiology / Q000517:prevention & control; D008175:Lung Neoplasms / Q000517:prevention & control* / Q000556:secondary*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008808:Mice, Inbred CBA; D009368:Neoplasm Transplantation; D011429:Propolis / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D011837:Radiation-Protective Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D012995:Solubility; D013997:Time Factors
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D011837:Radiation-Protective Agents; D015251:Epirubicin; D011429:Propolis