Occurrence of the Crabtree effect in HeLa cells

Melo, Roberto F.; Stevan-Hancke, F.R.; Campello, Annibal P.; Carnieri, Eva Gunilla Skare; Oliveira, Maria Benigna Martinelli de

doi:10.1002/(sici)1099-0844(199806)16:2<99::aid-cbf773>3.0.co;2-2

Cited by 12 publications

(6 citation statements)

References 25 publications

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“…In addition, the accumulation of some intermediate metabolites, such as serine, phosphoribosyl-pyrophosphate, fructose 1,6-bisphosphate, and glycerol 3-phosphate, can trigger the mitogenic events. [9][10][11] Although the alterations of glucose utilization and hypoxia in tumors are complicated biochemical processes, their clinical reflections will be a cornerstone on the therapeutic approach. Therefore, the data regarding the Pasteur Effect or the Crabtree Effect on tumor cell lines may help to evaulate the success of a given treatment.…”

Section: Introductionsupporting

confidence: 74%

Effects Of Thalidomide And rhGM-CSF on Carbohydrate Metabolism In HL-60 Acute Promyelocytic Leukemia Cell Line

Boyunağa¹

2011

UHOD

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The purpose of this study is to investigate the in vitro effect of thalidomide and rhGM-CSF on energy metabolism rate in HL-60 cell lines. HL-60 cells were incubated with radiolabelled glucose for 4 hours. Following incubation, radiolabelled CO2 was isolated and collected in specially designed scintillation vials. The other end-products of carbohydrate catabolism collected via anion-exchange chromatography were analyzed using liquid scintillation. Protein and glycogen levels for each group were also determined. The study results indicated that the use of drugs for 2-days had no significant effect when compared with aerobic and anaerobic controls. However, groups treated with the drugs for 5 days showed significant differences. It was obvious that rhGM-CSF caused HL-60 leukemia cells to use aerobic glycolytic pathway for production of energy. When thalidomide and rhGM-CSF combination therapy results were compared with untreated control cells, it was observed that glycogen consumption was decreased by 50.37%, and CO2 production was increased by 94.03%. When compared with those of anaerobic controls, glycogen consumption and CO2 production rates were found to be decreased by 54.01% and increased by 96.59%, respectively. As a consequence, we found that those cell lines treated with combined use of Thalidomide and rhGM-CSF caused HL-60 leukemia cells to predominantly prefer aerobic glycolytic pathways for energy production.Keywords: Thalidomide, Metabolism, rhGM-CSF, HL-60 cell line ÖZET HL-60 Akut Promyelositik Lösemi Hücre Kültürlerinde Thalidomide ve rhGM-CSF Kullan›lmas›n›n Karbonhidrat Metabolizmas›na EtkileriBu çal›flma, HL-60 hücre kültürlerinde in vitro olarak thalidomide ve rhGM-CSF uygulamas›n›n enerji metabolizmas›na etkilerini araflt›rma amac› ile yap›ld›. HL-60 hücre kültürleri radyoaktif glukozla 4 saat inkübe edildi. Ard›ndan radioaktif iflaretli CO2 özel sintilasyon viallerinde topland›, karbonhidrat katabolizmas›n›n di¤er son ürünleri ise anyon de¤iflim kromotografisi ile ayr›ld› ve s›v› sintilasyon arac›l›¤›yla analiz edildi. Ayr›ca her grubun protein ve glikojen düzeyleri ölçüldü. ‹ki günlük ilaç kullan›m› aerobik ve anaerobik kontrollerde anlaml› bir fark oluflturmazken befl günlük ilaç kullan›m›nda anlaml› fark oldu¤u tespit edildi. rhGM-CSF uygulanan HL-60 lösemi hücre kültürlerinin aerobik glikolitik yola kayd›¤› belirlendi. Thalidomide ve rhGM-CSF kombine tedavisinin sonuçlar›, ilaç verilmeyen aerobik kontrol grubuyla karfl›laflt›r›ld›¤›nda glikojen tüketiminin %50.37 azald›¤›, CO2 üretiminin ise %94.03 oran›nda artt›¤› belirlendi. Kombine ilaç verilen grup anaerobik kontrolle karfl›laflt›r›ld›¤›nda ise, glikojen tüketiminin %54.01 azald›¤›, CO2 üre-timin ise %96.59 artt›¤› belirlendi. Sonuç olarak Thalidomide ve rhGM-CSF kombine kullan›ld›¤›nda, HL-60 lösemi hücrelerinin enerji üretiminde esas olarak aerobik glikolitik yolu tercih ettikleri belirlendi.Anahtar Kelimeler: Talidomit, Metabolizma, rhGM-CSF, HL-60 hücre serisi ULUSLARARASı HEMATOLOJI-ONKOLOJI DERGISI ARTICLE

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Section: Introductionsupporting

confidence: 74%

Effects Of Thalidomide And rhGM-CSF on Carbohydrate Metabolism In HL-60 Acute Promyelocytic Leukemia Cell Line

Boyunağa¹

2011

UHOD

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“…In ascites tumor cells, the Crabtree effect is strong, as exogenous glucose inhibits the OxPhos flux by 60–80% through a multi‐site mechanism involving changes in the intracellular pH and Pi content (Rodríguez‐Enríquez et al, 2001). OxPhos of HeLa monolayer cells is also sensitive to glucose inhibition although to a lower extent than ascites cells (Melo et al, 1998). Therefore, the most appropriate physiological condition to determine OxPhos should be in the presence of physiological glucose.…”

Section: Discussionmentioning

confidence: 99%

Novel paclitaxel‐eluting, biodegradable polymer coated stent in the treatment of de novo coronary lesions: A prospective multicenter registry

Buszman

Trznadel

Milewski

et al. 2007

Cathet Cardio Intervent

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Objectives: The purpose of the present study was to evaluate the efficacy and safety of a biodegradable polymer coated, paclitaxel eluting stent (Luc-Chopin 2 ) based on 9-months angiographic and 12-months clinical follow-up results. Background: First-generation drug-eluting stents utilize nonbioabsorbable polymeric coatings, whose persistent presence in the arterial wall may negatively affect long-term outcomes. Bioabsorbable coatings with a degradation period matched to that of the drug elution may be a better alternative, clinically and economically. Methods: We conducted a prospective, multicenter first-in-man registry of a novel, locally developed, bioabsorbable-coated, paclitaxel-eluting coronary stent in 116 patients with single-lesion de novo coronary disease. Results: Major adverse cardiac events occurred in 7.8% patients within 12 months. There were no late thrombotic events, death, stroke, or surgical revascularization in that period. There were two myocardial infarctions, one related to recent subacute stent thrombosis and another associated with restenosis. By 12 months, target vessel revascularization was performed in 7.8%; 2.9% were ischemia-driven and the rest were mandated at 9 months in accordance with a control angiography protocol. Core-lab assessed binary in-stent restenosis (≥50% DS) was noted in 11.9% patients and mean late loss was 0.46 6 0.47 mm. Conclusions: This first-in-man experience obtained in a multicenter registry of real-world de novo lesions (almost half of lesions were class B2 or C by AHA classification) showed a favorable safety profile and acceptable efficacy through 12 months. Randomized comparison with a benchmark nonbioabsorbable polymer coated paclitaxel eluting stent should be undertaken to validate this initial positive experience. '

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“…Partial inhibition of oxidative phosphorylation by the addition of glucose and other hexoses in fast‐growth tumor cells (Table 1) [64,80–85] and normal, proliferative cells (hamster and neural rat embryos and rat thymocyte proliferating cells) is well documented [86,87]. After glucose addition in AS‐30D cells the glycolytic flux elevates, but the ATP and P i contents decrease and the cytosolic pH lowers from 7.2 to 6.8; in addition, the concentrations of phosphorylated hexoses (G6P, fructose‐6‐phosphate, fructose‐1,6‐bisphosphate) show a substantial increase [64].…”

Section: Isoform Expression and Activitymentioning

confidence: 99%

Energy metabolism in tumor cells

et al. 2007

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In early studies on energy metabolism of tumor cells, it was proposed that the enhanced glycolysis was induced by a decreased oxidative phosphorylation. Since then it has been indiscriminately applied to all types of tumor cells that the ATP supply is mainly or only provided by glycolysis, without an appropriate experimental evaluation. In this review, the different genetic and biochemical mechanisms by which tumor cells achieve an enhanced glycolytic flux are analyzed. Furthermore, the proposed mechanisms that arguably lead to a decreased oxidative phosphorylation in tumor cells are discussed. As the O2 concentration in hypoxic regions of tumors seems not to be limiting for the functioning of oxidative phosphorylation, this pathway is re‐evaluated regarding oxidizable substrate utilization and its contribution to ATP supply versus glycolysis. In the tumor cell lines where the oxidative metabolism prevails over the glycolytic metabolism for ATP supply, the flux control distribution of both pathways is described. The effect of glycolytic and mitochondrial drugs on tumor energy metabolism and cellular proliferation is described and discussed. Similarly, the energy metabolic changes associated with inherent and acquired resistance to radiotherapy and chemotherapy of tumor cells, and those determined by positron emission tomography, are revised. It is proposed that energy metabolism may be an alternative therapeutic target for both hypoxic (glycolytic) and oxidative tumors.

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Occurrence of the Crabtree effect in HeLa cells

Cited by 12 publications

References 25 publications

Effects Of Thalidomide And rhGM-CSF on Carbohydrate Metabolism In HL-60 Acute Promyelocytic Leukemia Cell Line

Effects Of Thalidomide And rhGM-CSF on Carbohydrate Metabolism In HL-60 Acute Promyelocytic Leukemia Cell Line

Novel paclitaxel‐eluting, biodegradable polymer coated stent in the treatment of de novo coronary lesions: A prospective multicenter registry

Energy metabolism in tumor cells

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