Redox cycling by motexafin gadolinium enhances cellular response to ionizing radiation by forming reactive oxygen species.

@article{Magda2001RedoxCB,
  title={Redox cycling by motexafin gadolinium enhances cellular response to ionizing radiation by forming reactive oxygen species.},
  author={Darren J Magda and Cheryl Lepp and Nikolay N. Gerasimchuk and I. Lee and Jonathan L. Sessler and Ao Lin and John E. Biaglow and R A Miller},
  journal={International journal of radiation oncology, biology, physics},
  year={2001},
  volume={51 4},
  pages={
          1025-36
        }
}
  • D. Magda, C. Lepp, +5 authors R. Miller
  • Published 2001
  • Medicine
  • International journal of radiation oncology, biology, physics
PURPOSE To examine the mechanism of radiation enhancement by motexafin gadolinium (Gd-Tex) in vitro. METHODS AND MATERIALS Oxidation of ascorbate and NADPH by Gd-Tex was evaluated in a neutral buffer. Growth inhibition of human uterine cancer cell line MES-SA was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) dye. Clonogenic assays were used to measure radiation response in MES-SA, A549 human lung carcinoma, E89, a CHO cell line variant deficient in glucose… Expand
Motexafin gadolinium: a redox active drug that enhances the efficacy of bleomycin and doxorubicin.
  • R. Miller, K. Woodburn, +5 authors D. Magda
  • Medicine, Biology
  • Clinical cancer research : an official journal of the American Association for Cancer Research
  • 2001
TLDR
In clonogenic assays using Rif-1 cells, MGd enhanced the activity of Bleo approximately 1000-fold, and this effect was shown to be mediated, in part, by MGd inhibition of potentially lethal damage repair. 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 and zinc induce oxidative stress responses and apoptosis in B-cell lymphoma lines.
TLDR
It is found that increased levels of oxidative stress and intracellular free zinc precede and correlate with cell cycle arrest and apoptosis and support a role for MGd in treatment of B-cell hematologic malignancies. 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
Effects of motexafin gadolinium on DNA damage and X-ray-induced DNA damage repair, as assessed by the Comet assay.
TLDR
Motexafin gadolinium altered the kinetics of single-strand break repair soon after irradiation but did not inhibit potentially lethal damage repair in EMT6 cells. Expand
Motexafin Gadolinium, a Tumor-selective Drug Targeting Thioredoxin Reductase and Ribonucleotide Reductase*
TLDR
MGd-induced enzymatic generation of reactive oxygen species by TrxR plus a powerful inhibition of RNR is demonstrated, which may explain the effects of the drug on cancer cells, which often overproduce TrXR and have induced RNR for replication and repair. 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-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 disrupts zinc metabolism in human cancer cell lines.
TLDR
Intracellular free zinc levels increased in response to treatment with MGd in the absence of exogenous zinc, indicating that MGd can mobilize bound intracellular zinc. Expand
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  • Medicine, Biology
  • Clinical cancer research : an official journal of the American Association for Cancer Research
  • 2001
TLDR
In clonogenic assays using Rif-1 cells, MGd enhanced the activity of Bleo approximately 1000-fold, and this effect was shown to be mediated, in part, by MGd inhibition of potentially lethal damage repair. Expand
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