Tigliane-type phorbols stimulate human melanocyte proliferation: potentially safer agents for melanocyte culture.
Previous studies have established that some phorbol compounds that are active in binding to protein kinase C (PKC) are also strong mitogens for human melanocytes in culture. Structure/activity studies on tigliane class phorbol compounds, which lack an oxygen at the 12 position, have shown that tumor-promoting activity can be diminished or abolished though retaining other biologic activities of phorbol compounds, including the ability to activate PKC. In this study, two tigliane class phorbol derivates [12 deoxyphorbol, 13 isobutyrate (DPIB) and 12 deoxyphorbol, 13 phenylacetate (DPPA)] were studied for their ability to stimulate melanocyte proliferation in a serum-free culture system based on MCDB 153 medium. Compared to the activity of phorbol 12-O-myristate, 13 acetate (PMA), a widely used tumor-promoting phorbol derivative, DPIB and DPPA were effective mitogens for human melanocytes. The importance of PKC activation in mitogenic modulation of human melanocytes is further supported by the stereospecific mitogenic activity of (-)Indolactam V, a PKC-activating compound structurally unrelated to phorbols. The use of the tigliane type phorbols DPIB and DPPA to stimulate growth of human melanocytes may provide safer compounds for laboratory or patient studies and may also provide further insights into the role of PKC activation in human melanocyte biology.
Cela
A
A
Laboratory for Investigative Dermatology, Rockefeller University, NY, NY 10021-6399.
Leong
I
I
Krueger
J
J
D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004789:Enzyme Activation; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007769:Lactams / Q000494:pharmacology; D008544:Melanocytes / Q000187:drug effects*; D010703:Phorbol Esters / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D013268:Stimulation, Chemical; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007211:Indoles; D007769:Lactams; D010703:Phorbol Esters; C039067:12-deoxyphorbol 13-isobutyrate; C029704:12-deoxyphorbolphenylacetate; C043969:indolactam V; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate