Vitamin C protects HL60 and U266 cells from arsenic toxicity

Karasavvas, Nicos; Cárcamo, Juan M.; Stratis, George; Golde, David W.

doi:10.1182/blood-2003-03-0772

Cited by 58 publications

(42 citation statements)

References 71 publications

(109 reference statements)

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“…We quantified peroxide-equivalents in ES cell medium, which had been spiked with increasing amounts of AA, or its oxidized intermediate, dehydroascorbic acid (DHA). Consistent with previous results [24], AA but not DHA, dosedependently increased peroxide levels in both high and low glucose medium, with 500 lM AA releasing $10 lM peroxide after incubation for 60 minutes (Fig. 4D).…”

Section: Resultssupporting

confidence: 92%

“…Although the mechanism of action was not addressed in their original publication [34], Takahashi et al suggested that the role of AA in cardiomyogenesis was unrelated to its intrinsic antioxidant properties, as other antioxidants failed to reproduce the effects in the experimental system. Paradoxically, AA has been shown to have pro-oxidant properties in the presence of transition metals found in tissue culture media [24]. We thought it reasonable to postulate that AA could remove the cardiomyocyte block in low glucose-differentiated EBs by increasing levels of ROS.…”

Section: Resultsmentioning

confidence: 93%

“…A standard curve was prepared by addition of known amounts of hydrogen peroxide (supplied with the kit) to full medium. Alternatively, intracellular ROS levels were monitored by Flow Cytometry using the ROS-specific dye, H 2 DCFDA as described [24].…”

Section: Measurement Of Rosmentioning

confidence: 99%

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Mitochondrial Reactive Oxygen Species Mediate Cardiomyocyte Formation from Embryonic Stem Cells in High Glucose

et al. 2010

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Accumulating evidence points to reactive oxygen species (ROS) as important signaling molecules for cardiomyocyte differentiation in embryonic stem (ES) cells. Given that ES cells are normally maintained and differentiated in medium containing supraphysiological levels of glucose (25 mM), a condition which is known to result in enhanced cellular ROS formation, we questioned whether this high glucose concentration was necessary for cardiomyocyte lineage potential. We show here that ES cells cultured in physiological glucose (5 mM), maintained their general stemness qualities but displayed an altered mitochondrial metabolism, which resulted in decreased ROS production. Furthermore, ES and induced pluripotent stem (iPS) cells differentiated in lower glucose concentrations failed to generate cardiomyocyte structures; an effect mimicked with antioxidant treatments using catalase, N-acetyl cysteine and mitoubiquinone, under high glucose conditions in ES cells. Molecular analysis revealed that ES cells differentiated in 5 mM glucose had reduced expression of the pro-cardiac NOX4 gene and diminished phosphorylation of p38 mitogen-activated protein kinase (MAPK), together with specific changes in the cardiac transcriptional network. These outcomes could be reversed by supplementation of low glucose cultures with ascorbic acid, paradoxically acting as a pro-oxidant. Furthermore, forced expression of an upstream p38 MAPK kinase (MKK6) could bypass the requirement for ROS during differentiation to cardiomyocytes under low glucose conditions, illustrating a key role for p38 in the cardiac differentiation program. Together these data demonstrate that endogenous ROS control is important for cardiomyocyte formation from ES cells, and furthermore that supraphysiological glucose, by supplying ROS, is absolutely required.

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Section: Resultssupporting

confidence: 92%

Section: Resultsmentioning

confidence: 93%

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Mitochondrial Reactive Oxygen Species Mediate Cardiomyocyte Formation from Embryonic Stem Cells in High Glucose

et al. 2010

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“…21,22 Although in vivo effects have been reported for this combination, 23 the observed additive toxicity may not be selective for cancer cells, and BSO itself has not been successfully developed for clinical use. Ascorbic acid (AA), a key antioxidant molecule, augments the toxicity of As 2 O 3 in vitro, 24,25 but controversy exists regarding its mechanism of action, 26 and its potential for utility in the clinic is under study.…”

Section: Introductionmentioning

confidence: 99%

Trolox enhances the anti-lymphoma effects of arsenic trioxide, while protecting against liver toxicity

et al. 2007

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Arsenic trioxide (As 2 O 3 ) is an effective therapy in acute promyelocytic leukemia (APL), but its use in other malignancies is limited by the higher concentrations required to induce apoptosis. We have reported that trolox, an analogue of a-tocopherol, increases As 2 O 3 -mediated apoptosis in a variety of APL, myeloma and breast cancer cell lines, while nonmalignant cells may be protected. In the present study, we extended previous results to show that trolox increases As 2 O 3 -mediated apoptosis in the P388 lymphoma cell line in vitro, as evidenced by decrease of mitochondrial membrane potential and release of cytochrome c. We then sought to determine whether this combination can enhance antitumor effects while protecting normal cells in vivo. In BDF 1 mice, trolox treatment decreased As 2 O 3 -induced hepatomegaly, markers of oxidative stress and hepatocellular damage. In P388 tumor-bearing mice, As 2 O 3 treatment prolonged survival, and the addition of trolox provided a further significant increase in lifespan. In addition, the combination of As 2 O 3 and trolox inhibited metastatic spread, and protected the tumor-bearing mice from As 2 O 3 liver toxicity. Our results suggest, for the first time, that trolox might prevent some of the clinical manifestations of As 2 O 3 -related toxicity while increasing its pro-apoptotic capacity and clinical efficacy in hematological malignancies.

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“…Arsenic is an environmental toxin but it has also been used in medicine as a therapeutic agent for more than 2400 years. [2] Inorganic arsenic is now a first choice cancer chemotherapeutic against certain leukemia. [3], [4] The US Food and Drug Administration (FDA) approved the use of Trisenox brand arsenic trioxide (As 2 O 3 ) for the treatment of acute promyelocytic leukemia in September 2000.…”

Section: Introductionmentioning

confidence: 99%

L-Ascorbic acid and α-Tocopherol to protect against arsenic trioxide induced oxidative stress in H9c2 cardiomyocytes

R.C¹,

Abhilash²,

Nair³

2014

IOSRJPBS

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Vitamin C protects HL60 and U266 cells from arsenic toxicity

Abstract: Although there is no compelling evidence that vitamin C has antitumor activity in humans, clinical trials are testing the hypothesis that ascorbic acid (AA) will enhance the efficacy of arsenic trioxide (As 2 O 3 ) in myeloma.

Cited by 58 publications

References 71 publications

Mitochondrial Reactive Oxygen Species Mediate Cardiomyocyte Formation from Embryonic Stem Cells in High Glucose

Mitochondrial Reactive Oxygen Species Mediate Cardiomyocyte Formation from Embryonic Stem Cells in High Glucose

Trolox enhances the anti-lymphoma effects of arsenic trioxide, while protecting against liver toxicity

L-Ascorbic acid and α-Tocopherol to protect against arsenic trioxide induced oxidative stress in H9c2 cardiomyocytes

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