RESUMO
The extensively used thiol antioxidants (dithiothreitol, glutathione, and N-acetylcysteine) in combination with hydroxycobalamine (vitamin B12) gain toxic activity in relation to human lymphocytic leukemia cell line HL60. Combined treatment with thiol and vitamin B12 was followed by early destabilization of lysosomes and apoptotic death of cells. The cytotoxic effect was abolished by caspase inhibitors. An iron-chelating agent deferoxamine partly prevented cell death, while lysosomal protease inhibitor pepstatin produced no protective effect.
Assuntos
Antioxidantes/farmacologia , Ferro/metabolismo , Lisossomos/metabolismo , Compostos de Sulfidrila/farmacologia , Vitamina B 12/farmacologia , Acetilcisteína/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Ditiotreitol/farmacologia , Glutationa/farmacologia , Humanos , Lisossomos/efeitos dos fármacosAssuntos
Acetilcisteína/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Vitamina B 12/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma de Células Escamosas , Linhagem Celular Tumoral , Dano ao DNA , DNA de Neoplasias/efeitos dos fármacos , DNA de Neoplasias/genética , DNA de Cadeia Simples/efeitos dos fármacos , DNA de Cadeia Simples/genética , Humanos , Cinética , Neoplasias Laríngeas , Peroxidação de Lipídeos/efeitos dos fármacos , Peróxidos Lipídicos/metabolismoRESUMO
We studied the prooxidant and cytotoxic action of thiols N-acetylcystein (NAC) and glutathione (GSH) combined with vitamin Bl2b. The synergism of action of the thiols and Bl2b resulted in human carcinoma cell damage was found. It was shown that GSH and NAC in physiological doses combined with Bl2b caused the initiation of apoptosis. It was established that prooxidant action of the thiols combined with vitamin Bl2b, i. e. generation and accumulation of hydrogen peroxide in culture medium, led to intracellular oxidative stress and injury of cell redox system. These effects were completely abolished by nonthiol antioxidants catalase and pyruvate. The chelators of iron phenanthroline and deferoxamine did not suppress the H2O2 accumulation in culture medium but significantly inhibited the cell death induced by the thiols combined with Bl2b. Therefore, the thiols GSH and NAC widely used as antioxidants, in combination with vitamin Bl2b show prooxidant characteristics and induce, with the participation of intracellular iron, apoptotic HEp-2 cell death.