EFFECTS OF SEQUENTIAL COMBINATIONS OF N-METHYLFORMAMIDE WITH ADRIAMYCIN ON CULTURED MELANOMA-CELLS (M14)

The effects of sequential combinations of N-methylformamide (NMF) with adriamycin (ADM) on a human melanoma cell line (M14) were investigate d. The results obtained can be summarized as follows: (i) When NMF was administered before ADM (NMF --> ADM), a decrease of ADM-induced cyto toxicity and intracellular ADM content was revealed. Conversely, the r everse combination (ADM --> NMF) produced a remarkable reduction of ce ll survival accompanied by a significant intracellular drug retention. (ii) The fluorescence microscopy revealed that in NMF- and in NMF --> ADM-treated cells the actin microfilament distribution appeared to be very similar to that in control cells. On the contrary, a disorganiza tion of the microfilament architecture was observed in ADM --> NMF-tre ated cells. (iii) The microtubule organization was significantly alter ed by NMF. This effect appeared to be even more evident in M14 cells t reated with the combination ADM --> NMF. (iv) Confocal microscopy obse rvations showed an intracytoplasmic retention of ADM in ADM --> NMF-tr eated cells. These findings suggest that the cytoskeletal changes indu ced by NMF might interfere with the ADM efflux mechanisms, accounting for the high drug level and low survival detected in ADM --> NMF-treat ed cells, (C) 1994 Academic Press, Inc.