DIFFERENTIAL-EFFECTS OF CRYPTOPORIC ACID-D AND ACID-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-mu-mol) and 5 mg (5.9-mu-mol), 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-mu-M 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.