Inhibition by ascorbic acid of apoptosis induced by oxidative stress in HL-60 myeloid leukemia cells

Witenberg, Bruria; Kalir, Henry H.; Raviv, Ziv; Kletter, Yehudith; Kravtsov, Vladimir; Fabian, Ina

doi:10.1016/s0006-2952(98)00351-7

Cited by 65 publications

(43 citation statements)

References 44 publications

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“…In this study, we sought to define the role of vitamin C in inhibiting the phosphorylation of IB␣ in a mechanistic manner. The importance of vitamin C as an intracellular antioxidant is well documented and inhibits cell death induced by hydrogen peroxide (12,37), apoptosis induced by FAS binding to CD95 (27), and DNA damage induced by oxidative stress (22). In addition to these functions, vitamin C is a cofactor for various enzymatic hydroxylation reactions (13,14).…”

Section: Conversion Of Aa To Dha By Oxidative Stress Inhibits Lucifermentioning

confidence: 99%

“…In plasma and cells, AA is a powerful antioxidant, quenching reactive oxygen species (ROS) and reactive nitrogen species (10,14). Intracellular vitamin C can prevent cell death and inhibit mutations induced by oxidative stress (12,22,37). During the process of quenching free radicals, ascorbate donates an electron, becoming the unstable intermediate ascorbyl radical that can be reversibly reduced back to ascorbate.…”

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confidence: 99%

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Vitamin C Is a Kinase Inhibitor: Dehydroascorbic Acid Inhibits IκBα Kinase β

Cárcamo

Pedraza

Bórquez-Ojeda

et al. 2004

Molecular and Cellular Biology

119

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Reactive oxygen species (ROS) are key intermediates in cellular signal transduction pathways whose function may be counterbalanced by antioxidants. Acting as an antioxidant, ascorbic acid (AA) donates two electrons and becomes oxidized to dehydroascorbic acid (DHA). We discovered that DHA directly inhibits IB␣ kinase ␤ (IKK␤) and IKK␣ enzymatic activity in vitro, whereas AA did not have this effect. When cells were loaded with AA and induced to generate DHA by oxidative stress in cells expressing a constitutive active IKK␤, NF-B activation was inhibited. Our results identify a dual molecular action of vitamin C in signal transduction and provide a direct linkage between the redox state of vitamin C and NF-B signaling events. AA quenches ROS intermediates involved in the activation of NF-B and is oxidized to DHA, which directly inhibits IKK␤ and IKK␣ enzymatic activity. These findings define a function for vitamin C in signal transduction other than as an antioxidant and mechanistically illuminate how vitamin C down-modulates NF-B signaling.

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Section: Conversion Of Aa To Dha By Oxidative Stress Inhibits Lucifermentioning

confidence: 99%

mentioning

confidence: 99%

Vitamin C Is a Kinase Inhibitor: Dehydroascorbic Acid Inhibits IκBα Kinase β

Cárcamo

Pedraza

Bórquez-Ojeda

et al. 2004

Molecular and Cellular Biology

119

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“…The production of intracellular reactive oxygen species such as superoxide and hydrogen peroxide was determined by a method based on the changes in fluorescence of DCFH-DA, an oxidation-sensitive fluorescence probe, following a previously published procedure (24,25). Briefly, the cell suspension was incubated in fresh serum-free RPMI 1640 medium with 2 M DCFH-DA at 37°C for 40 min under continuous stirring.…”

Section: Measurement Of Intracellular Reactive Oxygen Species Productionmentioning

confidence: 99%

Inhibition of H2 Histamine Receptor-Mediated Cation Channel Opening by Protein Kinase C in Human Promyelocytic Cells

Suh

Lee

Jun

et al. 2001

The Journal of Immunology

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Histamine, through H2 receptors, triggers a prominent rise in intracellular free Ca2+ concentration ([Ca2+]i) in addition to an elevation of cAMP level in HL-60 promyelocytes. Here we show that the histamine-induced [Ca2+]i rise was due to influx of Ca2+ from the extracellular space, probably through nonselective cation channels, as incubation of the cells with SKF 96365 abolished the histamine-induced [Ca2+]i rise, Na+ influx, and membrane depolarization. The Ca2+ influx was specifically inhibited by pretreatment of the cells with PMA or extracellular ATP with 50% inhibitory concentrations of 0.12 ± 0.03 nM and 185 ± 17 μM, respectively. Western blot analysis of protein kinase C (PKC) isoforms revealed that PMA (≤1 nM) and ATP (300 μM) caused selective translocation of PKC-δ to the particulate/membrane fraction. Costimulation of the cells with histamine and SKF 96365 partially reduced histamine-induced granulocytic differentiation, which was evaluated by looking at the extent of fMet-Leu-Phe-induced [Ca2+]i rise and superoxide generation. In conclusion, nonselective cation channels are opened by stimulation of the H2 receptor, and the channels are at least in part involved in the induction of histamine-mediated differentiation processes. Both effects of histamine were selectively inhibited probably by the δ isoform of PKC in HL-60 cells.

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“…35,36) For example, hydrogen peroxide can induce apoptosis, 37,38) and thus it is a necessary element of anticancer drug-induced apoptosis. 39) Superoxide anion is also involved in apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Direct Reaction between Shikonin and Thiols Induces Apoptosis in HL60 Cells.

Gao

Hiromura

Yasui

et al. 2002

Biological & Pharmaceutical Bulletin

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Shikonin (b b-alkannin), a naphthoquinone compound, was found to induce apoptotic features such as chromatin condensation, DNA fragmentation, and activation of caspase 3 in HL60 cells. The mechanism was examined in terms of oxidative stress in the cells. Exposure of the cells to shikonin greatly reduced the total thiols, protein thiols, and glutathione levels, however, lipid peroxide levels were enhanced. The depletion of thiol levels in the cells was thus thought to induce lipid peroxidation and DNA fragmentation. An electron spin resonance study revealed that shikonin reacts directly with glutathione and other oxidative stress-relevant compounds in the lysate of HL60 cells. Pretreatment of such cells with N-acetylcysteine before shikonin treatment completely inhibited the DNA fragmentation. From these results, it was proposed that the chemical reaction between shikonin and cellular thiols such as glutathione and protein thiols induces apoptosis in HL60 cells.

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Inhibition by ascorbic acid of apoptosis induced by oxidative stress in HL-60 myeloid leukemia cells

Cited by 65 publications

References 44 publications

Vitamin C Is a Kinase Inhibitor: Dehydroascorbic Acid Inhibits IκBα Kinase β

Vitamin C Is a Kinase Inhibitor: Dehydroascorbic Acid Inhibits IκBα Kinase β

Inhibition of H2 Histamine Receptor-Mediated Cation Channel Opening by Protein Kinase C in Human Promyelocytic Cells

Direct Reaction between Shikonin and Thiols Induces Apoptosis in HL60 Cells.

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