Mitochondrial dysfunction is responsible for the intestinal calcium absorption inhibition induced by menadione

Marchionatti, Ana Maria Estivalete; Pérez, Adriana; Barboza, Gabriela E. Díaz de; Pereira, B. M. I.; Talamoni, Nori G. Tolosa de

doi:10.1016/j.bbagen.2007.10.020

Cited by 30 publications

(19 citation statements)

References 27 publications

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“…Menadione participates in redox cycling reactions catalyzed by a number of flavo‐enzymes, and its reduction at complex I of the mitochondrial respiratory chain interferes with mitochondrial respiration [20]. Menadione also induces ATP depletion, an increase of intracellular calcium with consequent apoptotic induction is indicated by cytochrome c release, DNA fragmentation [21], loss of mitochondrial membrane potential, cytoskeletal damage, blebbing and morphological alterations [22]. Menadione strongly inhibits the activities of glucose‐6‐phosphate dehydrogenase and glyceraldehyde‐3‐phosphate dehydrogenase [23].…”

Section: Resultsmentioning

confidence: 99%

New insights into redox response modulation in Fanconi’s anemia cells by hydrogen peroxide and glutathione depletors

Cuccarolo

Viaggi

Degan³

2012

The FEBS Journal

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Fanconi’s anemia (FA) patients face severe pathological consequences. Bone marrow failure, the major cause of death in FA, accounting for as much as 80–90% of FA mortality, appears to be significantly linked to excessive apoptosis of hematopoietic cells induced by oxidative stress. However, 20–25% of FA patients develop malignancies of myeloid origin. A survival strategy for bone marrow and hematopoietic cells under selective pressure evidently exists. This study reports that lymphoblastoid cell lines derived from two FA patients displayed significant resistance to oxidative stress induced by treatments with H2O2 and various glutathione (GSH) inhibitors that induce production of reactive oxygen species, GSH depletion and mitochondrial membrane depolarization. Among the various GSH inhibitors employed, FA cells appear particularly resistant to menadione (5 μm) and ethacrynic acid (ETA, 50 μm), two drugs that specifically target mitochondria. Even after pre‐treatment with buthionine sulfoximine, a GSH synthesis inhibitor that induces enhanced induction of reactive oxygen species, FA cells maintain significant resistance to these drugs. These data suggest that the resistance to oxidative stress and the altered mitochondrial and metabolic functionality found in the FA mutant cells used in this study may indicate the survival strategy that is adopted in FA cells undergoing transformation. The study of redox and mitochondria regulation in FA may be of assistance in diagnosis of the disease and in the care of patients.

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Section: Resultsmentioning

confidence: 99%

New insights into redox response modulation in Fanconi’s anemia cells by hydrogen peroxide and glutathione depletors

Cuccarolo

Viaggi

Degan³

2012

The FEBS Journal

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“…It is known that both drugs dissipate the mitochondrial membrane potential and alter the mitochondrial permeability with release of proapoptotic compounds [6,29]. In addition, MEN diminishes the activity of oxidoreductases from the intestinal Krebs cycle, which depresses the electron respiratory chain and the oxidative phosphorylation [29].…”

Section: Discussionmentioning

confidence: 99%

Antiproliferative action of menadione and 1,25(OH)2D3 on breast cancer cells

Marchionatti

Picotto

Narvaez

et al. 2009

The Journal of Steroid Biochemistry and Molecular Biology

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“…Fluorescence intensity of DiOC 6 was analyzed in a BD FACSCantoII flow cytometer with excitation and emission settings of 484 and 500 nm, respectively, and the results were analyzed using the FACSDiva software [31]. After treatments, cells (2 Â 10 5 ) were resuspended in 500 ml of PBS containing 40 nmol/l DiOC 6 and incubated in the dark for 15 min at 371C.…”

Section: Mitochondrial Membrane Potentialmentioning

confidence: 99%

Oxidative stress, cell cycle arrest and differentiation contribute toward the antiproliferative action of BSO and calcitriol on Caco-2 cells

et al. 2014

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The prognosis and incidence of colon cancer are linked to vitamin D3 serum levels. To evaluate the effects of D,L-buthionine-S,R-sulfoximine (BSO), 1,25(OH)2D3 and their combination on intestinal Caco-2 cell growth, to elucidate the possible cellular mechanisms involved in their antiproliferative action, and to determine whether BSO acts as a sensitizer to 1,25(OH)2D3 treatment, enabling minimization of the toxic effects caused by high doses of the steroid. Human colon cancer Caco-2 cells were treated with 1,25(OH)2D3, BSO, both, or vehicle. Cell proliferation was evaluated by crystal violet staining. Cell cycle and mitochondrial membrane potential were measured by flow cytometry. Total glutathione, catalase, superoxide dismutase, superoxide anion levels, and alkaline phosphatase activities were analyzed by spectrophotometry. DNA fragmentation was evaluated using the terminal dUTP nick end labeling assay. BSO and 1,25(OH)2D3 inhibited Caco-2 cell growth, an effect that was higher with the combined treatment. The antiproliferative effect produced by the combination could be protected by ascorbic acid. BSO plus 1,25(OH)2D3 induced cell cycle arrest and suppressed cell division. Total glutathione decreased and superoxide anion increased with BSO and BSO plus 1,25(OH)2D3. Catalase activity increased with the combined treatment. Mitochondrial membrane potential and alkaline phosphatase activity were altered by 1,25(OH)2D3 alone or plus BSO. The percentage of terminal dUTP nick end labeling-positive cells was increased. BSO increases the antiproliferative effect of 1,25(OH)2D3 on Caco-2 cells through induction of oxidative stress, which occurs simultaneously with DNA breakage. The antioxidant system can partially compensate the damage induced by BSO plus 1,25(OH)2D3. Cell differentiation induction is also involved in the response to the combined treatment.

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Mitochondrial dysfunction is responsible for the intestinal calcium absorption inhibition induced by menadione

Cited by 30 publications

References 27 publications

New insights into redox response modulation in Fanconi’s anemia cells by hydrogen peroxide and glutathione depletors

New insights into redox response modulation in Fanconi’s anemia cells by hydrogen peroxide and glutathione depletors

Antiproliferative action of menadione and 1,25(OH)2D3 on breast cancer cells

Oxidative stress, cell cycle arrest and differentiation contribute toward the antiproliferative action of BSO and calcitriol on Caco-2 cells

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