Menadione (vitamin K-3) enhances the mitogenic signal of epidermal growth factor via extracellular signal-regulated kinases

The effects of vitamin K-3 (VK3) on DNA synthesis, cell proliferation and m itogen-activated protein kinase pathway were investigated in G0-arrested NI H 3T3 fibroblasts. VK3 (5 mu M) alone stimulates DNA synthesis by 40% and m oderately increases the mitogenic effects of EGF, which is preceded by a ra pid phosphorylation of the extracellular signal-regulated kinases (ERKs). A t 20 mu M, VK3 had an antiproliferative effect. VK3 alone (5 and 50 mu M) o r in concert with EGF increases the activity of ERK2 (by 2.5 and 5 fold, re spectively). Our studies demonstrate that the activation of ERKs by VK3 alo ne, or VK3 plus EGF can promote either stimulatory or inhibitory effects on the mitogenic signal.