Antimelanoma activities of chimeric thiazole-androstenone derivatives

The discovery of chimeric anti-melanoma agents is reported. These molecules are potent growth suppressors of melanoma cells in vitro with growth inhibition of 50% (GI(50)) values as low as 1.32 mu M. Compounds were more toxic to melanoma cells in vitro than commonly used anti-melanoma agent dacarbazine as measured by TUNEL assay. They induced both caspase-independent apoptosis evident by colocalization of TUNEL with endonuclease G (EndoG) and caspase-mediated apoptosis measured by colocalization of TUNEL with caspase-activated DNase (CAD). In addition, compounds 3 and 5 strongly induced oxidative injury to melanoma cells as measured by TUNEL colocalization with heme oxygenase-1 (HO1). Dacarbazine induced only caspase-independent apoptosis, which may explain why it is less cytotoxic to melanoma cells than compounds 3, 4 and 5.

Automated summary

The discovery of chimeric anti-melanoma agents with potent growth suppressor effects on melanoma cells was reported. These agents induced cell apoptosis through multiple pathways and showed greater cytotoxicity to melanoma cells compared to the commonly used agent dacarbazine.