p53 regulates cyclophosphamide teratogenesis by controlling caspases 3, 8, 9 activation and NF-κB DNA binding

Pekar, Olga; Molotski, Nataly; Savion, Shoshana; Fein, Amos; Toder, V.; Torchinsky, Arkady

doi:10.1530/rep-07-0086

Cited by 27 publications

(24 citation statements)

References 44 publications

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“…In vivo, p53 activation in experimentally diabetic adult animals, as well as in embryo of pregnant diabetic rats, has been previously documented [30][31][32][33][34]. Upregulation of p53 was found associated with enhanced nonrenal [30] and renal cell [32][33][34] apoptosis.…”

Section: Discussionmentioning

confidence: 72%

Hyperglycemia alters renal cell responsiveness to pressure in a model of malignant hypertension

Efrati

Berman²,

Tov³

et al. 2009

Journal of Hypertension

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Hyperglycemic environment alters responsiveness of renal cells to in-vitro simulation of malignant hypertension. The main consequence of either malignant hypertension or hyperglycemia is exaggerated apoptosis. However, the operating mechanisms differ: Malignant hypertension stimulates renal cell apoptosis via increased angiotensin-II, whereas hyperglycemia elicits apoptosis via augmented p53. By contrast to pressure-induced excessive proliferation of normoglycemic cells, hyperglycemia prohibits elevated proliferation in response to pressure. Angiotensin-II production is maximally augmented by hyperglycemic environment and is not stimulated further by pressure application.

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Section: Discussionmentioning

confidence: 72%

Hyperglycemia alters renal cell responsiveness to pressure in a model of malignant hypertension

Efrati

Berman²,

Tov³

et al. 2009

Journal of Hypertension

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“…By inducing the release of mitochondrial cytochrome-c, p53 might be able to activate effector caspases, including caspase-3. Caspase-3, -8, and -9 may be the apoptotic effector machinery engaged by p53 to mediate teratogen-induced apoptotic pathways (Takaoka et al, 2003;Pekar et al, 2007).…”

Section: 9655 Roles Of P53 and Caspases In Induction Of Apoptosis Inmentioning

confidence: 99%

Roles of p53 and Caspases in Induction of Apoptosis in MCF-7 Breast Cancer Cells Treated with a Methanolic Extract of Nigella Sativa Seeds

Alhazmi

Hasan²,

Shafi³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Background: Nigella Sativa (NS) is an herb from the Ranunculaceae family that exhibits numerous medicinal properties and has been used as important constituent of many complementary and alternative medicines (CAMs). The ability of NS to kill cancer cells such as PC3, HeLa and hepatoma cells is well established. However, our understanding of the mode of death caused by NS remains nebulous. The objective of this study was to gain further insight into the mode and mechanism of death caused by NS in breast cancer MCF-7 cells. Materials and Methods: Human breast cancer cells (MCF-7) were treated with a methanolic extract of NS, and a dose-and time-dependent study was performed. The IC 50 was calculated using a Cell Titer Blue ® viability assay assay, and evidence for DNA fragmentation was obtained by fluorescence microscopy TUNEL assay. Gene expression was also profiled for a number of apoptosis-related genes (Caspase-3, -8, -9 and p53 genes) through qPCR. Results: The IC 50 of MCF-7 cells was 62.8µL/mL. When MCF-7 cells were exposed to 50 µL/mL and 100 µL/mL NS for 24h, 48h and 72h, microscopic examination (TUNEL assay) revealed a dose-and time-dependent increase in apoptosis. Similarly, the expression of the Caspase-3, -8, -9 and p53 genes increased significantly according to the dose and time. Conclusions: NS induced apoptosis in MCF-7 cells through both the p53 and caspase pathways. NS could potentially represent an alternative source of medicine for breast cancer therapy.

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“…Our recent study revealed that CP-induced excessive apoptosis is also mediated by p53 and, importantly, that p53 mediates CP-induced suppression of NF-κB DNA binding [91]. These data suggest that Loeken's model can legitimately be used to explain both diabetes-induced suppression of NF-κB activity and the function of TNFα as a protector against diabetes-induced teratogenic stress.…”

Section: Possible Mechanisms Underlying the Tnfα-regulated Response Tmentioning

confidence: 86%

TNFalpha in the Pathogenesis of Diabetes-Induced Embryopathies: Functions and Targets

Torchinsky¹,

Toder²

2007

Rev Diabet Stud

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■ AbstractHyperglycemia-induced increase in the production of reactive oxygen species (ROS) is proposed to be an initial step in the pathogenesis of diabetes-induced spontaneous abortions and structural inborn anomalies. However, the subsequent steps in this process are incompletely understood. One of the key molecules involved is tumor necrosis factor-alpha (TNFα): its expression is regulated by ROS and it regulates ROS production in turn. This cytokine has been the focus of many studies addressing the mechanisms of different forms of diabetes-induced embryopathies, such as early pregnancy loss, inborn anomalies, fetal growth retardation as well as some pathologies appearing during adult life. In this review, we analyze the results of these studies and discuss how TNFα may regulate the response of pre-and postimplantation stage embryos to diabetes-induced detrimental stimuli. The data presented in this review suggest that TNFα may play a dual role in the pathogenesis of diabetes-induced embryopathies. It may act both as a mediator of diabetesinduced embryotoxic stimuli leading to the death of periimplantation stage embryos and, possibly, as a suppressor of diabetes-induced apoptosis in post-implantation stage embryos. It also appears that TNFα fulfills these functions via interaction with leukemia inhibitory factor (LIF) and the transcription factor NF-κB. These molecules are presently considered as attractive targets for the treatment of diabetesinduced complications. Therefore, further studies addressing their role in the mechanisms underlying diabetes-induced embryopathies are needed to evaluate the safety of such therapies for diabetic women of childbearing age.

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p53 regulates cyclophosphamide teratogenesis by controlling caspases 3, 8, 9 activation and NF-κB DNA binding

Cited by 27 publications

References 44 publications

Hyperglycemia alters renal cell responsiveness to pressure in a model of malignant hypertension

Hyperglycemia alters renal cell responsiveness to pressure in a model of malignant hypertension

Roles of p53 and Caspases in Induction of Apoptosis in MCF-7 Breast Cancer Cells Treated with a Methanolic Extract of Nigella Sativa Seeds

TNFalpha in the Pathogenesis of Diabetes-Induced Embryopathies: Functions and Targets

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