Inhibition of Spontaneous Hepatocarcinogenesis by 4,5-Didehydrogeranylgeranoic Acid: Effects of Small-Dose and Infrequent Administration

Abstract

Inhibitory effects of 4,5-didehydrogeranylgeranoic acid (dGGA) on the development of tumors were investigated in spontaneous hepatoma mice, C3H/HeNCrj. Experiment 1: Male mice at 8 weeks of age were raised on a basal diet, and then provided with a diet containing 0.02% dGGA from 32 to 91 weeks of age. Experiment 2: dGGA was administered to the animals only once at different time points, from 2 months to 17 months after birth, respectively. Experiment 3: dGGA was administered twice to the mice at different time points: at 5 months and 11 months, and at 8 months and 11 months, respectively. When the inhibitory effects on tumor development were evaluated with the incidences of tumors, average numbers, and weight of tumors per mouse, there was a marked relationship between the time of single or dual dosing and the inhibitory effects of dGGA. The greatest inhibitory effects were observed in Experiment 3 in the group of animals given dGGA at the ages of 8 and 11 months, which were far superior to the results with a large dose of the compounds for a long time. These results might indicate that dGGA administered at the right time in the right amount effectively prevents the development of cancer.