We previously reported that combined treatment with melphalan and mild hyperthermia (1 h at 42°C) caused a synergistic cytotoxic effect in JR8 melanoma cells, paralleled by a stabilisation of a melphalan induced G2-phase cell block. In this study, we investigated the effect of melphalan and hyperthermia on proteins that regulate G2-M transition. Neither hyperthermia nor melphalan at a concentration 2.5 μg ml-1, which had no antiproliferative effect at 37°C, interfered with cyclin B1 expression or p34(cdc2) kinase activity. At a concentration of 8.5 μg ml-1, which reduced cell growth by 50% at 37°C, melphalan inhibited p34(cdc2) kinase activity as a consequence of an increased tyrosine phosphorylation of the protein. A similar inhibitory effect on p34(cdc2) kinase was obtained when the lowest melphalan concentration (2.5 μg ml-1) was used under hyperthermic conditions. Our results indicate that thermal enhancement of melphalan cytotoxicity could be mediated at least in part by an inhibition of p34(cdc2) kinase activity, which prevents cell progression into mitosis.
|Number of pages||5|
|Journal||British Journal of Cancer|
|Publication status||Published - 1996|
- Cyclin B
- G-M transition
ASJC Scopus subject areas
- Cancer Research