N-Chloroamino acids mediate the action of hypochlorite on A549 lung cancer cells in culture.
Hypochlorous acid, a chlorinating and oxidative agent, has been reported to be implicated in many pathologies. Its markers were found under inflammatory conditions and, at least some of it reveals biological activity. Thus, in this paper we examined whether N-chloroamino acids may act as mediators of the action of hypochlorous acid in cell culture. N-Chloroamino acids were found to possess lower oxidative capacity than HOCl/OCl(-) just after addition to the growth medium. However, all the chlorocompounds studied were cytotoxic to A549 cells, induced a dose-dependent increase in the G(0)/G(1) fraction with simultaneous reduction in the G(2)/M fraction, collapse of the mitochondrial potential and caspase-dependent apoptosis. The content of cellular thiols decreased after 1-h incubation with the chlorocompounds studied. Although amino acids act as scavengers of hypochlorite in plasma, the chlorinated products formed stay reactive and the pattern of their action on cells in vitro is similar to that of hypochlorite.
Department of Molecular Biophysics, University of Łódź, Banacha 12/16, 90-237 Łódź, Poland. agnieszka.robaszkiewicz@gmail.com
Agnieszka
A
Robaszkiewicz
Grzegorz
G
Bartosz
Mirosław
M
Soszyński
D000230:Adenocarcinoma / Q000473:pathology*; D000596:Amino Acids / Q000737:chemistry*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003470:Culture Media; D004273:DNA, Neoplasm / Q000096:biosynthesis; D006801:Humans; D006997:Hypochlorous Acid / Q000633:toxicity*; D008175:Lung Neoplasms / Q000473:pathology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009336:Necrosis / Q000473:pathology; D016877:Oxidants / Q000378:metabolism / Q000494:pharmacology*
D000596:Amino Acids; D003470:Culture Media; D004273:DNA, Neoplasm; D016877:Oxidants; D006997:Hypochlorous Acid; D053148:Caspase 3