Canventol inhibits tumor promotion in CD-1 mouse skin through inhibition of tumor necrosis factor alpha release and of protein isoprenylation.
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.
Komori
A
A
Cancer Prevention Division, National Cancer Center Research Institute, Tokyo, Japan.
Suganuma
M
M
Okabe
S
S
Zou
X
X
Tius
M A
MA
Fujiki
H
H
D016475:3T3 Cells; D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D003511:Cyclohexanols / Q000494:pharmacology*; D004224:Diterpenes / Q000494:pharmacology; D004988:Ethers, Cyclic / Q000494:pharmacology; D005260:Female; D008798:Mevalonic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D051379:Mice; D019319:Okadaic Acid; D017368:Protein Prenylation / Q000187:drug effects*; D012878:Skin Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D016588:Anticarcinogenic Agents; D003511:Cyclohexanols; D004224:Diterpenes; D004988:Ethers, Cyclic; D014409:Tumor Necrosis Factor-alpha; C082453:canventol; D019319:Okadaic Acid; C058761:sarcophytol A; D015127:9,10-Dimethyl-1,2-benzanthracene; C015367:mevalonolactone; D008798:Mevalonic Acid