Published in Cancer Detection and Prevention 1998; 22(6):506-515.

Apoptosis and Suppression of Tumor Growth by Artepillin C Extracted From Brazilian Propolis

Tetsuo Kimoto, M.D., Ph.D.,a Shigeyuki Arai, D.V.M., Ph.D.,a Michihiro Kohguchi, B.S., a Miho Aga, B.Pharm.,a Yutaka Nomura, B.S., a Mark J. Micallef, Ph.D.,a Masashi Kurimoto, M.S.,a and Keiichiro Mito, Ph.D.b

a Fujisaki Institute, Hayashibara Biochemical Laboratories, Okayama, Japan; and b Kawasaki College of Allied Health Professions, Kurashiki, Japan.

Address all correspondence and reprint requests to: Tetsuo Kimoto, M.D., Ph.D., Fujisaki Institute, Hayashibara Biochemical Laboratories Inc., Fujisaki 675-I, Okayama 702, Japan.

ABSTRACT: 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 human and murine malignant tumor cells in vitro and in vivo, artepillin C exhibited a cytotoxic effect and the growth of tumor cells was clearly 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 in vitro. When xenografts of human tumor cells were transplanted into nude mice, the cytotoxic effects of artepillin C were most noticeable in carcinoma and malignant melanoma. Apoptosis, abortive mitosis, and massive necrosis combined were identified by histological observation after intratumor injection of 500 μg of artepillin C three times a week. In addition to suppression of tumor 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 artepillin C activates the immune system, and possesses direct antitumor activity.

KEY WORDS: antitumor activity, apoptosis, artepillin C, macrophages, propolis.