Motexafin gadolinium reacts with ascorbate to produce reactive oxygen species.

@article{Magda2002MotexafinGR,
  title={Motexafin gadolinium reacts with ascorbate to produce reactive oxygen species.},
  author={Darren J Magda and Nikolay N. Gerasimchuk and Philip S. Lecane and Richard A. Miller and John E. Biaglow and Jonathan L. Sessler},
  journal={Chemical communications},
  year={2002},
  volume={22},
  pages={
          2730-1
        }
}
Motexafin gadolinium (MGd) oxidizes ascorbate, in neutral buffer and in cell culture, forming reactive oxygen species and a coordination polymer with oxalate. 
Ascorbate and endocytosed Motexafin gadolinium induce lysosomal rupture.
TLDR
It is proposed that subsequent apoptosis is a synergistic effect of irradiation and high MGd concentrations in malignant cells due to their pronounced endocytic activity, and provides novel insights into the mode of action of this promising anti-cancer drug. Expand
Activation of Platinum(IV) Prodrugs By Motexafin Gadolinium as a Redox Mediator.
TLDR
The present "activation by reduction" approach may allow for the cancer-selective enhancement in the cytotoxicity of Pt(IV) prodrugs. Expand
Motexafin gadolinium generates reactive oxygen species and induces apoptosis in sensitive and highly resistant multiple myeloma cells.
TLDR
Intacellular uptake of MGd and intracellular ROS production were found, and MGd induced apoptosis in fresh malignant cells from patients with multiple myeloma and related disorders, providing a rationale for clinical investigation of this novel redox-mediating agent. Expand
Motexafin Gadolinium-Induced Cell Death Correlates with Heme oxygenase-1 Expression and Inhibition of P450 Reductase-Dependent Activities
TLDR
It is reported that hematopoietic-derived cell lines that constitutively express HO1 are more susceptible to MGd-induced apoptosis than those that do not, and its in vitro inhibition of a broad spectrum of P450 enzymes indicates that a potential exists for drug-drug interactions. Expand
Motexafin gadolinium induces mitochondriallymediated caspase-dependent apoptosis
TLDR
The results demonstrating differential sensitivity of drug-induced apoptosis to caspase inhibitors suggest that the term “caspase-independent apoptosis” cannot be solely defined as apoptosis that is not inhibited by z-VAD-fmk as has been utilized in some published studies. Expand
Motexafin gadolinium: a novel redox active drug for cancer therapy.
TLDR
Combining MGd treatment with ionizing radiation improves time to neurologic progression in lung cancer patients with brain metastases and the molecular target for MGd appears to be thioredoxin reductase which, when inhibited, results in cellular redox stress, cytotoxicity and an increase in tumor responsiveness to a variety of treatments. Expand
Motexafin gadolinium induces oxidative stress and apoptosis in hematologic malignancies
TLDR
Motexafin gadolinium (MGd) is a synthetic expanded porphyrin that selectively accumulates in tumor cells and oxidizes various intracellular metabolites, including ascorbate, nicotinamide adenine dinucleotide phosphate, glutathione, and protein thiols, to generate reactive oxygen species in a process known as futile redox cycling. Expand
Texaphyrins and water-soluble zinc(II) ionophores: development, mechanism of anticancer activity, and synergistic effects
TLDR
The basic properties of texaphyrins and the zinc ionophores they helped spawn will be discussed in the cadre of developing an understanding that could lead to the preparation of new, redox-active anticancer agents. Expand
Oxalate production via oxidation of ascorbate rather than reduction of carbon dioxide
TLDR
It is shown that the oxalate is produced not by reduction of CO2, but by reaction of ascorbate with oxygen, and the previously published results might have eventuated from oxygen contamination of the reaction mixtures utilised for the labelling studies and the UV/Vis spectroscopic study. Expand
Motexafin gadolinium enhances p53-Mdm2 interactions, reducing p53 and downstream targets in lymphoma cell lines.
TLDR
The data are consistent with a pathway of cell death that is independent of p53-mediated induction of PUMA; the cellular response to reduce p53 represents a cell survival adjustment to ROS-mediated stress. Expand
...
1
2
3
4
...

References

SHOWING 1-10 OF 14 REFERENCES
Redox cycling by motexafin gadolinium enhances cellular response to ionizing radiation by forming reactive oxygen species.
TLDR
Gd-Tex sensitizes cells to ionizing radiation by increasing oxidative stress as a consequence of futile redox cycling and optimization of the concentration of ascorbate (or other reducing species) may be required when evaluating Gd- Tex activity in vitro. Expand
Catalytic metals, ascorbate and free radicals: combinations to avoid.
TLDR
This presentation discusses the role of catalytic metals in free radical-mediated oxidations, ascorbate as both a pro-oxidant and an antioxidant, use of asCorbate to determine adventitious catalytic metal concentrations, and uses of ascorBate radical as a marker of oxidative stress. Expand
Pulse radiolytic studies of metallotexaphyrins in the presence of oxygen: Relevance of the equilibrium with superoxide anion to the mechanism of action of the radiation sensitizer motexafin gadolinium (Gd-Tex2+, xcytrin)
Pulse radiolytic studies of aqueous solutions of four representative metallotexaphyrin complexes M−Tex2+ (M = Gd(III), Lu(III), Dy(III), and Y(III)), carried out in the presence of either dioxygen,Expand
Ascorbate-enhanced Cytotoxicity of misonidazole
TLDR
The effect of ascorbic acid (vitamin C) on the cytotoxicity of misonidazole is shown, which shows that it leads to strand breaks in cellular DNA and those cells which fail to survive also fail to repair these strand breaks. Expand
Ascorbate metabolism and its regulation in animals.
TLDR
The authors deal with the synthesis and the breakdown of ascorbate as a part of the antioxidant and carbohydrate metabolism, and a complex metabolic regulation is supposed. Expand
One-electron reduction and oxidation studies of the radiation sensitizer gadolinium(III) texaphyrin (PCI-0120) and other water soluble metallotexaphyrins
The radiation sensitizer gadolinium(III) texaphyrin 2 (XYTRIN; PCI-0120; Gd−Tex2+) and several other water soluble metallotexaphyrin complexes were prepared and studied using pulse radiolysis. All ofExpand
The pecking order of free radicals and antioxidants: lipid peroxidation, alpha-tocopherol, and ascorbate.
  • G. Buettner
  • Chemistry, Medicine
  • Archives of biochemistry and biophysics
  • 1993
TLDR
Using one-electron reduction potentials, the predicted pecking order is in agreement with experimentally observed free radical electron (hydrogen atom) transfer reactions and suggests that vitamin E, the primary lipid soluble small molecules antioxidant, and vitamin C, the terminal water soluble small molecule antioxidant, cooperate to protect lipids and lipid structures against peroxidation. Expand
A microplate assay for the detection of oxidative products using 2',7'-dichlorofluorescin-diacetate.
TLDR
This assay can be useful for screening monoclonal antibodies recognizing cell surface structures possibly involved in signal transduction as well as for testing phagocytes for their capacity to release reactive oxidative intermediates. Expand
The importance of peroxide and superoxide in the X-ray response.
TLDR
The data suggest that GSH depletion results in the inhibition of cellular GSHTase before it inhibits GSH peroxidase, therefore, part of the increased aerobic radiation response maybe due to cellular inability to reduce hydroperoxides. Expand
Effects of Motexafin gadolinium on tumor metabolism and radiation sensitivity.
TLDR
If metabolic changes induced by Motexafin gadolinium (Gd-Tex(+2), XCYTRIN) predict time intervals between drug and radiation wherein there is enhancement of radiation efficacy, then NMR spectroscopy may be useful for monitoring tumor metabolism after treatment with Gd- Tex (+2) and administering radiation during the time of maximal efficacy of Gd -Tex(-2). Expand
...
1
2
...