کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2130442 1086573 2013 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Metabolic changes during ovarian cancer progression as targets for sphingosine treatment
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Metabolic changes during ovarian cancer progression as targets for sphingosine treatment
چکیده انگلیسی


• During ovarian cancer progression, cells become more glycolytic.
• Changes in the TCA flux generate substrates for fatty acid and cholesterol biosynthesis.
• During progression, the mitochondria show a decreased maximum respiration rate.
• Exogenous sphingosine targets citrate synthase, TCA flux, glycolysis and cholesterol biosynthesis.

Tumor cells often exhibit an altered metabolic phenotype. However, it is unclear as to when this switch takes place in ovarian cancer, and the potential for these changes to serve as therapeutic targets in clinical prevention and intervention trials. We used our recently developed and characterized mouse ovarian surface epithelial (MOSE) cancer progression model to study metabolic changes in distinct disease stages. As ovarian cancer progresses, complete oxidation of glucose and fatty acids were significantly decreased, concurrent with increases in lactate excretion and 3H-deoxyglucose uptake by the late-stage cancer cells, shifting the cells towards a more glycolytic phenotype. These changes were accompanied by decreases in TCA flux but an increase in citrate synthase activity, providing substrates for de novo fatty acid and cholesterol synthesis. Also, uncoupled maximal respiration rates in mitochondria decreased as cancer progressed. Treatment of the MOSE cells with 1.5 μM sphingosine, a bioactive sphingolipid metabolite, decreased citrate synthase activity, increased TCA flux, decreased cholesterol synthesis and glycolysis. Together, our data confirm metabolic changes during ovarian cancer progression, indicate a stage specificity of these changes, and suggest that multiple events in cellular metabolism are targeted by exogenous sphingosine which may be critical for future prevention trials.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Cell Research - Volume 319, Issue 10, 10 June 2013, Pages 1431–1442
نویسندگان
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