Selective Inhibition of Growth and Respiration of Melanomas by Tyrosinase Inhibitors2

Abstract

A segment of respiration in pigmented human melanomas can be depressed in vitro by phenyl lactate, a tyrosinase inhibitor. Amelanotic human and nonpigmented S91 melanomas do not have a portion of respiration sensitive to this agent. The phenyl lactate-sensitive segment may be vital to pigmented melanoma melanocytes because the Pasteur effect is released when this segment is depressed. B16 mouse melanomas, which are very fast growing, heavily pigmented tumors, are resistant to phenyl lactate alone, but when treated very briefly with chilling or transient anaerobiosis become susceptible to it. This segment of respiration fn the human and mouse melanomas may represent tyrosinase activity, which furthermore may be vital to melanoma melanocyte respiration in vitro. Tissue culture growth studies revealed that phenyl lactate could also selectively prevent pigmented melanoma growth. The correlations between the Warburg and tissue culture studies suggest that tyrosinase may be necessary for the growth in vitro of melanoma melanocytes.