Stimulation of DNA synthesis in untransformed cells by the antiviral and antitumoral compound tricyclodecan-9-yl-xanthogenate (D609)

The antiviral and antitumor xanthate compound tricyclodecan-9-yl-xanthogenate (D609) is best known for its inhibitory effect on phosphatidylcholine-specific phospholipase C activity. Now we report that in NIH 3T3 cells, but not in several transformed cell types tested, D609 stimulated DNA synthesis when phosphocholine (PCho), insulin, or ATP was also present. Maximal co-mitogenic effects of D609 were observed at 5 mu g/mL, a concentration 4-6 times lower than that required to inhibit phospholipase C activity. The synergistic mitogenic effects of D609 and PCho, but not of D609 and insulin, were associated with activation of p42 and, to a lesser extent, p44 mitogen-activated protein (MAP) kinases. The results raise the possibility that the mitogenic activity of D609 in untransformed cells may contribute to its antiviral and antitumor effects. (C) 1998 Elsevier Science Inc.