Antitumor and Anticytopenic Effects of Aqueous Extracts of Propolis in Combination with Chemotherapeutic Agents

Ikukatsu Suzuki,1 Ikuo Hayashi,1 Takayuki Takaki,1 Debra S. Groveman,2 and Yoshiaki Fujimiya3,4

1Department of Clinical Nutrition, Faculty of Health Sciences, Suzuka University of Medical Science, Suzuka, Mie 510-0293, Japan; 2Veterans Administration Hospital, White River Junction, VT 05009, U.S.A.; 3Department of Basic Medical Sciences, IOND University, Tokyo 165-0027, Japan; and 4R&D Department, Nimura Genetic Solutions, Tokyo 151-051, Japan.


Using an ICR mouse model bearing a syngeneic Ehrlich ascitis carcinoma, the present study was under- taken to examine the effects of crude, water-soluble propolis (CWSP) on tumor progression, chemother- apeutic efficacy, and hematopoiesis in the peripheral blood. It was demonstrated that CWSP, adminis- tered subcutaneously, resulted in marked regression of tumor growth in mice, at the early phase after tumor inoculation (CWSP, p , 0.05 vs. saline control). Molecular analysis indicated that the CWSP is composed of 8.4% protein, 4.2% quercetin plus a variety of saccharides with a molecular weight of 29 kDa. Orally administered CWSP did not produce any regression for the observation period (oral CWSP, p . 0.05 vs. saline control). Peritoneal injection of CWSP into neonatal mice resulted in an increased lymphocyte/polymorphonuclear leukocyte ratio activity, indicating the potential activation of lymphoid cell lineages. These observations suggest that subcutaneously injected CWSP could regulate the devel- opment of tumors by possibly stimulating multicellular immunity. In addition, oral administration of CWSP concurrently with 5-fluorouracil (5-FU) or mitomycin C (MMC), significantly increased tumor regression as compared with the respective chemotherapy alone, illustrating the adjuvant effect of orally adminis- tered CWSP for tumor regression when combined with chemotherapeutic agents.

To examine further the potential usefulness of CWSP for chemotherapeutic regimens, which induce pro- found multilineage hematopoietic suppression, mice that received CWSP orally in addition to a 5-FU or MMC were followed for absolute numbers of platelets and white and red blood cells. The oral adminis- tration of CWSP significantly ameliorated the cytopenia induced by 5-FU, resulting in recovery of white as well as red blood cell counts (5-FU plus CWSP, p , 0.05 vs. 5-FU alone or water control; white blood cells on day 15, red blood cells on day 25), but no marked effects on platelet counts was observed (5-FU plus CWSP, p . 0.05 vs. 5-FU alone or water control). On the other hand, CWSP significantly reduced all three MMC-induced cytopenias, especially at the later stage of the chemotherapeutic course (after day 30), suggesting repetitive requirements of oral administration of CWSP.

In summary, subcutaneous administration of an aqueous CWSP resulted in marked regression of trans- planted tumors. Orally administered CWSP combined with chemotherapeutic agents significantly in- creased tumor regression and ameliorated the cytopenia induced by the chemotherapeutic agents alone. These results suggest the benefits of potential clinical trials using CWSP combined with chemotherapeu- tic agents in order to maximize enhanced immunity while potentially minimizing postchemotherapeutic deteriorated reactions.