Differential effects of cryptoporic acids D and E, inhibitors of superoxide anion radical release, on tumor promotion of okadaic acid in mouse skin.
Cryptoporic acids D and E, isolated from the fungus Cryptoporus volvatus, are inhibitors of superoxide anion radical release. Cryptoporic acid E inhibited tumor promotion of okadaic acid in two-stage carcinogenesis experiments on mouse skin, initiated with 7,12-dimethylbenz[a]anthracene. Treatment with cryptoporic acid E using two different doses per application, 1 (1.2 mumol) and 5 mg (5.9 mumol), reduced the percentage of tumor-bearing mice from 73.3 to 53.3% and 20.0%, and the average number of tumors per mouse from 4.2 to 2.3 and 0.5 respectively in week 20 of tumor promotion. However, cryptoporic acid D slightly enhanced tumor promotion rather than inhibition of okadaic acid. Cryptoporic acid D was expected to have additional biochemical activities, such as activation of protein kinases. Cryptoporic acid D at concentrations of up to 100 microM activated protein kinase C and stimulated other protein kinase activity in vitro, whereas cryptoporic acid E did not. These two compounds provided differential effects on tumor promotion of okadaic acid on mouse skin.
Matsunaga
S
S
Cancer Prevention Division, National Cancer Center Research Institute, Tokyo, Japan.
Furuya-Suguri
H
H
Nishiwaki
S
S
Yoshizawa
S
S
Suganuma
M
M
Hashimoto
T
T
Asakawa
Y
Y
Fujiki
H
H
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D002273:Carcinogens; D004789:Enzyme Activation / Q000187:drug effects; D004988:Ethers, Cyclic / Q000633:toxicity*; D005260:Female; D005609:Free Radicals; D051379:Mice; D019319:Okadaic Acid; D011493:Protein Kinase C / Q000032:analysis; D011494:Protein Kinases / Q000032:analysis; D012717:Sesquiterpenes / Q000494:pharmacology*; D012878:Skin Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D013481:Superoxides / Q000378:metabolism*
D002273:Carcinogens; D004988:Ethers, Cyclic; D005609:Free Radicals; D012717:Sesquiterpenes; D013481:Superoxides; C069196:cryptoporic acid D; C069197:cryptoporic acid E; D019319:Okadaic Acid; D015127:9,10-Dimethyl-1,2-benzanthracene; D011494:Protein Kinases; D011493:Protein Kinase C