engleski

Effects of propolis on tumor growth and metastasing ability ; a possible mode of antitumor action

We have studied the antimestatic efficacy of water-soluble derivate of Brazilian or Croatian propolis (WSDP) and compared it with either antimetastatic effect of caffeic acid phenethyl ester (CAPE) or with caffeic acid (CA), a propolis-derived compounds. In vitro cytotoxicity of these compounds on tumor cells were also studied. Tumor was a transplantable mammary carcinoma (MCA) of spontaneous origin, weakly immunogenic to a syngenic CBA mouse. Metastases in the lung were generated by injecting 200 000 viable tumor cells iv. Tested compounds were given po or ip before or after tumor cell inoculation ; the dose comprises 50 mg/kg. In in vitro studies V79 cells, HeLa cells or MCA cells were used ; the concentration of WSDP, CAPE and CA were 25 mg/ml, 5 mg/ml and 25 mg/ml, respectively. Ingestions of propolis significantly reduced the number of tumor nodules in the lung of mice. The antimetastatic effectiveness of WSDP was of higher degree than that achieved by either CAPE or CA. In in vitro studies WSDP did not affect the growth of cells, while CAPE and CAPE and CA expressed strong cytotoxic effect. Two aproaches for testing possible mode of antimetastatic activity in the lungs were proposed: a modulation of immune reaction of recipients or induction of apoptosis during the formation of metastatic nodules. Changes in several immunological parametars such as the response of lymphocytes to polyclonal mitogens in vitro, production of TNF by lymphoid cells and IL-1 by peritoneal macrophages, and rosette formation of lymphoid cells with SRBC, respectively, correlated well with antimetastatic properties of tested compounds. A direct relationship was also found between antimetastatic activity of compounds studied and induction of apoptosis.

tumor; metastases; propolis

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