A synthetic compound named
canventol, 2-isopropyl-4-isopropylidencyclohex-2-ene-1-ol, inhibited
tumor promotion of
okadaic acid on mouse skin initiated with
7,12-dimethylbenz(a)anthracene in two-stage
carcinogenesis experiments more strongly than
sarcophytol A, isolated from a soft coral, although
canventol has a simpler structure than
sarcophytol A. Their mechanisms of action were studied based on our recent evidence that
tumor necrosis factor alpha release induced by
okadaic acid is an essential mechanism of
tumor promotion.
Canventol inhibited mouse
tumor necrosis factor alpha release from BALB/3T3 cells less strongly than
sarcophytol A, indicating that
canventol has additional activity.
Canventol inhibited isoprenylation of
proteins with various molecular weights, such as M(r) 22,000, 17,000, and 13,000, whereas
sarcophytol A did not show significant inhibition. Thus, a potent anticarcinogenic activity of
canventol is mediated through the inhibitory bifunctions of
tumor necrosis factor alpha release and of protein isoprenylation. Since
canventol is less toxic to cells than
sarcophytol A, these bifunctions are useful markers for screening for new
cancer chemopreventive agents.