APOPTOSIS AND SUPPRESSION OF TUMOR-GROWTH BY ARTEPILLIN-C EXTRACTED FROM BRAZILIAN PROPOLIS

Artepillin C was extracted from Brazilian propolis. Artepillin C (3,5- diprenyl-4-hydroxycinnamic acid) has a molecular weight of 300.40 and possesses antibacterial activity. When artepillin C was applied to hum an and murine malignant tumor cells in vitro and in vivo, artepillin C exhibited a cytotoxic effect and the growth of tumor cells was clearl y inhibited. The artepillin C was found to cause significant damage to solid tumor and leukemic cells by the MTT assay, DNA synthesis assay, and morphological observation irt vitro. When xenografts of human tum or cells were transplanted into nude mice, the cytotoxic effects of ar tepillin C were most noticeable in carcinoma and malignant melanoma. A poptosis, abortive mitosis, and massive necrosis combined were identif ied by histological observation after intratumor injection of 500 mu g of artepillin C three times a week. In addition to suppression of tum or growth, there was an increase in the ratio of CD4/CD8 T cells, and in the total number of helper T cells. These findings indicate that ar tepillin C activates the immune system, and possesses direct antitumor activity.