Selective induction of apoptosis by capsaicin in transformed cells: the role of reactive oxygen species and calcium.
Capsaicin is a vanilloid quinone analog that inhibits the plasma membrane electron transport (PMOR) system and induces apoptosis in transformed cells. Using a cytofluorimetric approach we have determined that capsaicin induces a rapid increase of reactive oxygen species (ROS) followed by a subsequent disruption of the transmembrane mitochondrial potential (DeltaPsim) and DNA nuclear loss in transformed cell lines and in mitogen activated human T cells. This apoptotic pathway is biochemically different from the typical one induced by either ceramide or edelfosine where, in our system, the DeltaPsim dissipation precedes the generation of reactive oxygen species. Neither production of ROS nor apoptosis was found in capsaicin-treated resting T cells where the activity of the PMOR system is minimal when compared with mitogen activated or transformed T cells. Capsaicin also induces Ca2+ mobilization in activated but not in resting T cells. However, preincubation of cells with BAPTA-AM, which chelate cytosolic free calcium, did not prevent ROS generation or apoptosis induced by capsaicin, suggesting that ROS generation in capsaicin treated cells is not a consequence of calcium signaling and that the apoptotic pathway may be separated from the one that mobilizes calcium. Moreover, we present data for the implication of a possible vanilloid receptor in calcium mobilization, but not in ROS generation. These results provide evidence that the PMOR system may be an interesting target to design antitumoral and anti-inflammatory drugs.
Macho
A
A
Departamento de Fisiología e Inmunología, Universidad de Córdoba, Spain.
Calzado
M A
MA
Muñoz-Blanco
J
J
Gómez-Díaz
C
C
Gajate
C
C
Mollinedo
F
F
Navas
P
P
Muñoz
E
E
D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism*; D002211:Capsaicin / Q000494:pharmacology*; D002453:Cell Cycle; D002461:Cell Line, Transformed; D004247:DNA / Q000378:metabolism; D004579:Electron Transport; D005292:Ferricyanides / Q000494:pharmacology; D006801:Humans; D019169:Jurkat Cells; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism; D010742:Phospholipid Ethers / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012402:Rotenone / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects*
D005292:Ferricyanides; D010742:Phospholipid Ethers; D017382:Reactive Oxygen Species; D012402:Rotenone; C007931:hexacyanoferrate III; C026659:edelfosine; D004247:DNA; D002211:Capsaicin; D002118:Calcium