Stimulation of alkaline phosphatase activity in mouse epidermis by tumor promoters

Complete as well as incomplete (second stage) tumor promoters increase alkaline phosphatase (AP) activity in mouse epidermis in vivo but not in vitro. This indicates that the high level of AP in epidermis after application of a tumor promoter arises from an extraepidermal site, possibly from leaky endothelial cells of promoter-damaged blood vessels. Quercetin, which is known to stabilize the microvasculature as well as to inhibit tumor promotion, very effectively suppresses tumor promoter-stimulated AP activity. Quercetin is also a potent inhibitor of calcium, phospholipid-dependent protein kinase (Ca, PL-PK). Since inhibitors of other enzymes also suppressible by quercetin are ineffective, the damage of microvasculature and the increase in AP activity in epidermis might be Ca, PL-PK mediated effects of tumor promoters.