Antimelanoma activities of chimeric thiazole–androstenone derivatives. Issue 8 (11th August 2021)

• Record Type: Journal Article
• Authors: Chambers, Steven A.; Newman, Mathew; Frangie, Melissa M.; Savenka, Alena V.; Basnakian, Alexei. G.; Alam, Mohammad A.
• Is Part Of: Royal Society open science. Volume 8:Issue 8(2021)
• Publication Date: 2021-08-11
• Subjects: melanoma -- thiazole -- androstenone -- flow cytometry -- apoptosis -- TUNEL assay; Science -- Periodicals; 500
• DOI: 10.1098/rsos.210395
• Languages: English
• ISSNs: 2054-5703

Abstract

Abstract : 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% (GI50 ) values as low as 1.32 µM. 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 .