STIMULATION OF DIFFERENTIATED FUNCTIONS IN HUMAN-MELANOMA CELLS BY TUMOR-PROMOTING AGENTS AND DIMETHYL-SULFOXIDE

  • 1 January 1979
    • journal article
    • research article
    • Vol. 39  (7) , 2618-2624
Abstract
Treatment of cultured human HO melanoma cells with the mouse skin tumor-promoter phorbol-12-myristate-13-acetate (PMA) at 5 .times. 10-10 to 5 .times. 10-7 M resulted in a dose-related inhibition of growth and a stimulation of differentiated functions. These included melanin systhesis and formation of dendrite-like structures. Higher doses of phorbol dibutyrate, less potent tumor promoter, were required to produce an effect comparable to that of PMA for dendrite induction. Phorbol and 2 other phorbol esters, which lack tumor-promoting activity, were either inactive or elicited a poor response. In addition to morphological changes, treatment with PMA altered glucosamine incorporation into membrane gangliosides. After PMA treatment, glucosamine incorporation increased 8- to 10-fold in the Gm3 ganglioside and decreased 2-fold in the GM1 ganglioside, as compared to phorbol or untreated control. Inhibition of cell growth and stimulation of melanin synthesis were also observed after treatment of the HO cells with dimethyl sulfoxide [DMS]. Unlike the tumor-promoting agents, DMS did not induce the formation of dendrite-like structures in the cells. HO melanoma cells can be stimulated into terminally differentiated cells after treatment with tumor-promoting agents such as phorbol diesters.