BENZODIAZEPINE-INDUCED INHIBITION OF HUMAN-MALIGNANT MELANOMA (M-6) CELL-GROWTH

Since benzodiazepines (BZs) have been shown to inhibit the growth of s ome cell lines, the effects of these drugs on human melanoma (M-6) cel l growth were examined. Cell growth was measured by the tetrazolium sa lt (MTT) assay or the Hoechst 33258 DNA assay. Diazepam, a non-selecti ve BZ agonist, and Ro5-4864, a peripheral-type agonist, inhibited M-6 cell proliferation by 36% and 55% with EC(50)s of 139 mu M and 107 mu M respectively, after four days of treatment in culture. The central-t ype agonists, clonazepam and flunitrazepam were ineffective. The antip roliferative effect of diazepam was partially reversed by treatment wi th phorbol 12-myristate 13-acetate (PMA). Neither PK 11195, a peripher al-type BZ receptor antagonist nor flumazenil a central-type antagonis t, blocked the effect of diazepam, indicating that these BZ receptors are not involved. The effect of PMA suggests that the antiproliferativ e effect of the BZs may involve inhibition of a calcium/protein kinase C-related pathway in M-6 cells.