Nitric oxide is synthesized in acute leukemia cells after exposure to phenolic antioxidants and initially protects against mitochondrial membrane depolarization.
We investigated the early events involved in loss of mitochondrial membrane potential (DeltaPsi(mt)) leading to apoptosis in cells derived from patients with acute lymphocytic leukemia after exposure to phenolic antioxidants. Using the nitric oxide binding dye diaminofluorescein-FM diacetate, we found that intracellular nitric oxide (NO) levels increased significantly within 4h after exposure to the antioxidants curcumin, carnosol, and quercetin. Inhibition of nitric oxide synthetase (NOS) activity with mercaptoethylguanidine increased the percentage of leukemia cells with depolarized mitochondria membranes after antioxidant treatment. These data suggest that NO production in the leukemia-derived cells may be a protective response to maintain DeltaPsi(mt) after antioxidant exposure and inhibition of NOS increases the disruption of mitochondrial homeostasis induced by the antioxidants.
Kellner
Christian
C
Friedrich-Alexander University of Erlangen-Nürnberg, D91058 Erlangen, Germany.
Zunino
Susan J
SJ
D045784:Abietanes; D000975:Antioxidants / Q000494:pharmacology*; D003474:Curcumin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010616:Phenanthrenes / Q000494:pharmacology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism* / Q000473:pathology; D011794:Quercetin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D045784:Abietanes; D000975:Antioxidants; D004791:Enzyme Inhibitors; D006146:Guanidines; D010616:Phenanthrenes; D009569:Nitric Oxide; C068623:carnosol; D011794:Quercetin; D019001:Nitric Oxide Synthase; D003474:Curcumin; C100078:2-mercaptoethylguanidine