Sarcophytols A and B inhibit tumor promotion by teleocidin in two-stage carcinogenesis in mouse skin

Abstract

Sarcophytols A and B, isolated from a soft coral, Sarcophyton glaucum, are cembrane-type diterpenes with different numbers of hydroxyl groups. Sarcophytols A and B inhibited tumor promotion by teleocidin in two-stage carcinogenesis experiments on mouse skin. The inhibitory effect of sarcophytol A was demonstrated with two different initiating doses of 7,12-dimethylbenz[a]anthracene (DMBA): 50 micrograms (experiment 1) and 100 micrograms (experiment 2). In experiment 1, three groups of mice were treated with DMBA, and then twice a week with doses (1.6 micrograms, 16 micrograms, and 82 micrograms) of sarcophytol A followed by 2.5 micrograms teleocidin. In week 25, the incidences of tumors in these groups were only 7.1%, 20.0%, and 13.3%, respectively, whereas that in the control group treated with DMBA plus teleocidin was 53.3%. Moreover, at this time, the average numbers of tumors per mouse in these groups were 0.1, 0.3, and 0.3, respectively, while that in the control group was 2.1. In experiment 2 an amount of sarcophytol A (1.6 micrograms) or B (1.7 micrograms) equimolar to 2.5 micrograms teleocidin was applied twice a week, as in experiment 1, and results showed that sarcophytol B also inhibited tumor promotion by teleocidin. Both sarcophytols A and B caused delay in onset of tumor formation, and reduced the percentage of tumor-bearing mice and the average number of tumors per mouse. The effective concentrations of sarcophytols A and B were in the microgram range with an equimolar amount of teleocidin.