Midori Takasaki

Inhibition of epstein-barr virus early antigen activation promoted by 12-O-tetradecanoylphorbol-13-acetate by the non-steroidal anti-inflammatory drugs.

As part of our screening program for cancer inhibitory agents effective specifically in the promotion stage of cancer development, we have evaluated the possible inhibitory effects of 36 non-steroidal anti-inflammatory drugs (NSAIDs) on the Epstein-Barr virus early antigen (EBV-EA) activation which was induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. All the drugs were observed to inhibit the EBV-EA activation at low doses with low toxicity. The two most active anti-tumor promoting agents were the arylacetic acid derivatives, etodolac and sulindac. We also report for the first time the activities of 14 new NSAIDs belonging to different classes as potential cancer chemopreventive agents. A structure-activity relationship study showed that among the salicylic acid derivative tested, the oxidation of the thiol group to dithiol derivatives results in the reduction of the activity. Introduction of amino group on the salicylic acid molecules also results in the reduction of activity in the EBV-EA assay. The results are of great interest in the development of NSAIDs as cancer chemopreventive agents, which halt cancer progression in multistage carcinogenesis, where successive activities are required to evolve into fully-fledged and metastatic cancer.

Abstract B72: Cancer chemopreventive potential of henna

Abstracts: Frontiers in Cancer Prevention Research 2008 B72 “Henna” is a powder of the leaves of Lawsonia inermis L. This powder is used mainly as a pigment for coloring skin, hair, fingernails, leather, silk and wool. The anticancer potential of henna powder was evaluated using in vitro and in vivo assays. Henna inhibited tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) - induced activation of Epstein-Barr virus early antigen in lymphoblastoid Raji cells. This indicated the anticancer potential of henna powder. The activity of henna powder was also studied in the ultraviolet B light (280-320 nm wavelength, 34.3 kJ/m2) - initiated and TPA- promoted two stage mouse skin carcinogenesis model. Topical application of a suspension of henna (0.5 mg/ml acetone) decreased tumor incidence in this model system by 70% and tumor multiplicity by 40% at ten weeks of treatment. Lawsone and its precursors 1, 2, 4-trihydroxynaphthalene-1,4-di-beta-glucopyranoside and 1, 2-dihydroxy-4-O-glucosyloxynaphthalene may be the pharmacologically active compounds in henna. In the present study lawsone inhibited TPA-induced activation of Epstein-Barr virus early antigen by 94%. The cancer inhibitory effect of topically applied henna powder was further demonstrated in the peroxynitrite (PN) -initiated and TPA - promoted two stage mouse skin carcinogenesis model system. In this model system, henna decreased tumor incidence by 55% and tumor multiplicity by 57% at 11 weeks of treatment. These data suggest that henna powder as well as its major coloring pigment, lawsone and/or its precursors may be useful as cancer preventive agents. The ability of lawsone and its precursors to perturb electron transfer reactions and free radical processes may partially account for their cancer preventive effects. Citation Information: Cancer Prev Res 2008;1(7 Suppl):B72.