Involvement of reactive oxygen species in capsaicinoid-induced apoptosis in transformed cells.
Some varieties of sweet pepper accumulate non-pungent isosters of capsaicin, a type of compounds exemplified by capsiate. The only structural difference between capsaicin and capsiate is the link between the vanillyl and the acyl moieties, via an amide bond in the former and via an ester bond in the latter. By flow cytometry analyses we have determined that nor-dihydrocapsiate, a simplified analogue of capsiate, is a pro-oxidant compound that induces apoptosis in the Jurkat tumor cell line. The nuclear DNA fragmentation induced by nor-dihydrocapsiate is preceded by an increase in the production of reactive oxygen species and by a subsequent disruption of mitochondria transmembrane potential. Capsiate-induced apoptosis is initiated at the S phase of the cell cycle and is mediated by a caspase-3-dependent pathway. The accumulation of intracellular reactive oxygen species in capsiate-treated cells is greatly prevented by the presence of ferricyanide, suggesting that capsiates target a cellular redox system distinct from the one involved in the mitochondrial electron-chain transport. Methylation of the phenolic hydroxyl of nor-dihydrocapsiate completely abrogated the ability to induce reactive oxygen species and apoptosis, highlighting the relevance of the presence of a free phenolic hydroxyl for the pro-oxidant properties of capsaicinoids.
Macho
Antonio
A
Departamento de Biología Celular, Fisiología e Inmunología, Facultad de Medicina, Universidad de Córdoba, Avda. de Menéndez Pidal s/n, 14004, Córdoba, Spain.
Sancho
Rocío
R
Minassi
Alberto
A
Appendino
Giovanni
G
Lawen
Alfons
A
Muñoz
Eduardo
E
D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002461:Cell Line, Transformed; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D004579:Electron Transport; D005292:Ferricyanides / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D019169:Jurkat Cells; D008564:Membrane Potentials; D008745:Methylation; D008928:Mitochondria / Q000378:metabolism; D008956:Models, Chemical; D010084:Oxidation-Reduction; D019800:Phenol; D017382:Reactive Oxygen Species / Q000378:metabolism*; D011955:Receptors, Drug / Q000378:metabolism; D016196:S Phase; D013997:Time Factors
D000975:Antioxidants; D005292:Ferricyanides; D017382:Reactive Oxygen Species; D011955:Receptors, Drug; C007931:hexacyanoferrate III; D019800:Phenol; D004247:DNA; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; C470213:capsiate; D002211:Capsaicin