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 e lectron transport (PMOR) system and induces apoptosis in transformed cells, Using a cytofluorimetric approach we have determined that capsaicin induce s a rapid increase of reactive oxygen species (ROS) followed by a subsequen t disruption of the transmembrane mitochondrial potential(BY,) and DNA nucl ear loss in transformed cell lines and in mitogen activated human T cells, This apoptotic pathway is biochemically different from the typical one indu ced by either ceramide or edelfosine where, in our system, the Delta Psi(m) dissipation precedes the generation of reactive oxygen species. Neither pr oduction of ROS nor apoptosis was found in capsaicin-treated vesting T cell s where the activity of the PMOR system is minimal when compared with mitog en activated or transformed T cells, Capsaicin also induces Ca2+ mobilizati on in activated but not in resting T cells. However, preincubation of cells with BAPTA-AM, which chelate cytosolic free calcium, did not prevent ROS g eneration or apoptosis induced by capsaicin, suggesting that ROS generation in capsaicin treated cells is not a consequence of calcium signaling and t hat the apoptotic pathway may be separated from the one that mobilizes calc ium. 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 desig n antitumoral and anti-inflammatory drugs.