Chemotherapy Influences Inducible Nitric Oxide Synthase (iNOS) and Endothelial Nitric Oxide Synthase (eNOS) Activity on 3D Breast Cancer Cell Line

Öktem, Gülperi; Bılır, Ayhan; Selvi, Nur; Yurtseven, Mine; Vatansever, Seda; Ateş, Utku; Uysal, Ayhan; Omay, Serdar Bedii

doi:10.3727/000000006783981107

Cited by 18 publications

(15 citation statements)

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“…The decrease in Arg that we found at low dose of DTX may reflect NO production and at high dose, may be a consequence of Glu excessive consumption. Actually, DTX was shown to enhance iNOS expression [15] and NO production [16] in breast cancer cells and through stimulation of p38 activity in alveolar macrophages [17]. NO also mediates sphingomyelinase activation and apoptotic process through ceramide production [48].…”

Section: Discussionmentioning

confidence: 99%

“…Metabolite kinetics (6,16,24,48,72, and 96 h) in response to clinical dose of DTX (5 lM) is shown in Fig. 3.…”

Section: Metabolomics Of Mcf7 Cell Response To Docetaxel At Clinical mentioning

confidence: 99%

“…Cells were exposed to 5 lM DTX, 1 nM DTX, or the vehicle (0.5% DMSO) for 6,12,16,24,36,48,72, and 96 h. After each treatment and before analysis, cells were washed twice with PBS (100 ll per well or 10-20 ml per flask) to remove detached and dead cells. The pH of each medium was measured.…”

Section: Cell Treatmentmentioning

confidence: 99%

“…Reactive oxygen and nitrogen species have been reported to be involved in taxane cytotoxicity [12,13], resulting from activation of NADPH oxidase [14]. Also DTX increased inducible nitric oxide synthase (iNOS) expression [15] and subsequent nitric oxide (NO) production [16] in breast cancer cells and through the stimulation of p38 activity in alveolar macrophages [17]. At low concentration (10 nM), DTX was shown to activate diacylglycerol (DAG) kinase, a lipid kinase that phosphorylates DAG into phosphatidic acid (PA) [18].…”

Section: Introductionmentioning

confidence: 99%

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Pharmacometabolomics of docetaxel-treated human MCF7 breast cancer cells provides evidence of varying cellular responses at high and low doses

Bayet-Robert

Morvan

Chollet

et al. 2009

Breast Cancer Res Treat

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There is growing evidence that docetaxel, a microtubule-targeting agent like the other taxane paclitaxel, induces dual cytotoxicity mechanism according to dose level. Postgenomics screening technologies are now more and more applied to the elucidation of drug response mechanisms. Proton nuclear magnetic resonance spectroscopy-based pharmacometabolomics was here applied to get further insight into the response of human MCF7 breast carcinoma cells to docetaxel at high (clinical, 5 lM) and low (1 nM) doses. The global response to both doses was evaluated by nuclear morphology and DNA content, the latter as an index of cell proliferation and DNA ploidy. High dose provoked long-lasting cell cycle arrest in mitosis during the first 48 h of exposure to treatment and severe decrease in DNA content followed by significant amount of cell death. In contrast, at low dose, no long-lasting cell cycle arrest was observed on micrographies, and DNA content was decreased but less than at high dose (P \ 0.05), without significant cell death. This response was compared to biochemical alteration assessed by pharmacometabolomics. Thirty metabolites were identified and quantified. Metabolite profiling at clinical dose revealed time-dependent disorders in derivatives of glycolysis, lipid metabolism and glutathione metabolism.Comparison between high and low doses was performed at 72 h and showed common traits including the accumulation of cytidinediphosphocholine (95.0 and 96.9, respectively, P \ 0.03), the decrease in phosphatidylcholine (90.3 and 90.2, respectively, P \ 0.03), and gluthathione (90.6 and 90.6, respectively, P \ 0.03). Despite that, significant dosedependent differences were found in 12 of 30 measured metabolites. Among them, the most discriminant metabolites were polyunsaturated fatty acids (ratio of high-to-low dose of 14.8, P \ 0.05), glutamate, myoinositol, and homocysteine (ratio \ 0.4, P \ 0.05). In addition, the mechanism for glutathione decrease was different. At high dose, it resulted from extensive consumption with precursor starvation (glutamate: -89%, P \ 0.05) and increased glutathione S-transferase activity (95, P \ 0.01), whereas at low dose, it resulted from glutathione biosynthesis blockade with homocysteine accumulation (?144%, P \ 0.03) and decreased glutathione S-transferase activity (-70%, P \ 0.01). Altogether, this pharmacometabolomics analysis provides further evidence of the varying cellular responses at high and low doses of docetaxel in MCF7 breast cancer cells. The authors Mathilde Bayet-Robert and Daniel Morvan equally contributed to this work.

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Section: Discussionmentioning

confidence: 99%

“…Metabolite kinetics (6,16,24,48,72, and 96 h) in response to clinical dose of DTX (5 lM) is shown in Fig. 3.…”

Section: Metabolomics Of Mcf7 Cell Response To Docetaxel At Clinical mentioning

confidence: 99%

Section: Cell Treatmentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Pharmacometabolomics of docetaxel-treated human MCF7 breast cancer cells provides evidence of varying cellular responses at high and low doses

Bayet-Robert

Morvan

Chollet

et al. 2009

Breast Cancer Res Treat

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“…Anti-cancer agents such as gold lotion have successfully demonstrated their anti-carcinogenic potential through the regulation of both iNOS and eNOS [125][126][127]. Yu et al [128] also elucidated the significance of eNOS as a seemingly promising strategy for targeting anti-androgen resistant prostate carcinoma.…”

Section: Possible Therapy Strategies Of Nos On Prostate Carcinomamentioning

confidence: 99%

Nitric Oxide Synthase in Male Urological and Andrologic Functions

Yu¹,

Li²,

Li³

et al. 2017

Nitric Oxide Synthase - Simple Enzyme-Complex Roles

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Nitric oxide (NO), a crucial signaling molecule, is synthesized by the nitric oxide synthase (NOS) enzyme. The significant effects of NOS are under exploration, and the roles of potential therapy targets for diseases of NOS are widely accepted. In this chapter, we summarized the important roles of NOS mainly on pathogenesis of prostate diseases, male infertility, erectile dysfunction and, addition, the potential therapeutic efficacies of NOS for those diseases.

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Phosphanegold(I) thiolates, Ph3PAu[SC(OR)=NC6H4Me-4] for R = Me, Et and iPr, induce apoptosis, cell cycle arrest and inhibit cell invasion of HT-29 colon cancer cells through modulation of the nuclear factor-κB activation pathway and ubiquitination

et al. 2015

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The phosphanegold(I) carbonimidothioates, Ph3PAu{SC(OR)=NC6H4Me-4} for R = Me (1), Et (2) and iPr (3), feature linear P-Au-S coordination geometries and exhibit potent in vitro cytotoxicity against HT-29 colon cancer cells in both monolayer and multi-cellular spheroid models (e.g., IC50 = 11.9 ± 0.4 and 20.3 ± 0.3 μM for 2, respectively). Both intrinsic and extrinsic pathways of apoptosis are demonstrated by human apoptosis PCR array analysis, caspase activities, DNA fragmentation and cell apoptotic assays. Compounds 1-3 induce an extrinsic pathway that leads to down-regulation of NFκB. Compound 2 also exhibits an extrinsic apoptotic pathway involving the activation of both p53 and p73, whereas 3 activates p53 only. Lys48- and Lys63-linked polyubiquitination are also promoted by 1-3. Each of cytotoxic Ph3PAu{SC(OR)=NC6H4Me-4}, for R = Me (1), Et (2) and iPr (3), induce an intrinsic apoptotic pathway as well as an extrinsic pathway leading to down-regulation of NFκB. Lys48- and Lys63-linked polyubiquitination are promoted by 1-3 and these are able to inhibit cell invasion and to suppress the activity of TrxR.

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Chemotherapy Influences Inducible Nitric Oxide Synthase (iNOS) and Endothelial Nitric Oxide Synthase (eNOS) Activity on 3D Breast Cancer Cell Line

Cited by 18 publications

References 0 publications

Pharmacometabolomics of docetaxel-treated human MCF7 breast cancer cells provides evidence of varying cellular responses at high and low doses

Pharmacometabolomics of docetaxel-treated human MCF7 breast cancer cells provides evidence of varying cellular responses at high and low doses

Nitric Oxide Synthase in Male Urological and Andrologic Functions

Phosphanegold(I) thiolates, Ph3PAu[SC(OR)=NC6H4Me-4] for R = Me, Et and iPr, induce apoptosis, cell cycle arrest and inhibit cell invasion of HT-29 colon cancer cells through modulation of the nuclear factor-κB activation pathway and ubiquitination

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