Hydroxychalcones induce apoptosis in B16-F10 melanoma cells via GSH and ATP depletion.
Searching for leading compounds of new drugs for cancer therapy, we studied the toxicity of 13 hydroxychalcones never tested before toward melanoma cell line (B16-F10). The compounds were obtained by aldolic condensation between aldehydes and hydroxylated acetophenones, in alkaline conditions. Three of them showed cytotoxicity to the cell line. Two of them induced mitochondrial GSH and ATP depletion and promoted cell death through apoptosis in melanoma cells. One of the compounds induced cell death through necrosis but did not significantly decrease the intracellular mitochondrial GSH and ATP levels in melanoma cells. The results suggest that the predominant factor for the activity is the molecule shape, and secondarily the number of hydroxyl groups.
Navarini
Andréia Lilian Formento
AL
Departamento de Ciências Farmacêuticas, Universidade Federal de Santa Catarina, Centro de Ciências da Saúde, Campus Trindade, CEP 88040-900, Florianópolis, SC, Brazil.
Chiaradia
Louise Domeneghini
LD
Mascarello
Alessandra
A
Fritzen
Márcio
M
Nunes
Ricardo José
RJ
Yunes
Rosendo Augusto
RA
Creczynski-Pasa
Tânia Beatriz
TB
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002599:Chalcone / Q000737:chemistry* / Q000494:pharmacology*; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005978:Glutathione / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008545:Melanoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D013055:Spectrophotometry, Infrared
D000970:Antineoplastic Agents; D002599:Chalcone; D000255:Adenosine Triphosphate; D005978:Glutathione