Fenofibrate induces ketone body production in melanoma and glioblastoma cells
| العنوان: | Fenofibrate induces ketone body production in melanoma and glioblastoma cells |
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| المؤلفون: | Anna Wilk, Paula Banks, Maja Grabacka, Anna Antończyk, Emilia Walczyk-Tytko, Krzysztof Reiss, Matthew Dean, Malgorzata Pierzchalska |
| المصدر: | Frontiers in Endocrinology, Vol 7 (2016) Frontiers in Endocrinology |
| بيانات النشر: | Frontiers Media S.A., 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, medicine.medical_specialty, beta-hydroxybutyrate, Endocrinology, Diabetes and Metabolism, 3-hydroxy-3-methylglutaryl-CoA synthetase 2, peroxisome proliferator-activated receptor alpha, 3-hydroxy-3-methylglutaryl-CoA synthetase 2 (HMGCS2), Biology, lcsh:Diseases of the endocrine glands. Clinical endocrinology, 03 medical and health sciences, Endocrinology, Downregulation and upregulation, Internal medicine, Neurosphere, Ketogenesis, medicine, Receptor, Original Research, Fenofibrate, lcsh:RC648-665, Peroxisome Proliferator-Activated Receptor (PPAR) alpha, 3. Good health, 030104 developmental biology, Cancer cell, Ketone bodies, Peroxisome proliferator-activated receptor alpha, Transketolase, Energy Metabolism, medicine.drug |
| الوصف: | Ketone bodies [beta-hydroxybutyrate (bHB) and acetoacetate] are mainly produced in the liver during prolonged fasting or starvation. bHB is a very efficient energy substrate for sustaining ATP production in peripheral tissues; importantly, its consumption is preferred over glucose. However, the majority of malignant cells, particularly cancer cells of neuroectodermal origin such as glioblastoma, are not able to use ketone bodies as a source of energy. Here, we report a novel observation that fenofibrate, a synthetic peroxisome proliferator-activated receptor alpha (PPARa) agonist, induces bHB production in melanoma and glioblastoma cells, as well as in neurospheres composed of non-transformed cells. Unexpectedly, this effect is not dependent on PPARa activity or its expression level. The fenofibrate-induced ketogenesis is accompanied by growth arrest and downregulation of transketolase, but the NADP/NADPH and GSH/GSSG ratios remain unaffected. Our results reveal a new, intriguing aspect of cancer cell biology and highlight the benefits of fenofibrate as a supplement to both canonical and dietary (ketogenic) therapeutic approaches against glioblastoma. |
| اللغة: | English |
| تدمد: | 1664-2392 |
| DOI: | 10.3389/fendo.2016.00005/full |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::74f1c9f647f5cde726a434e582d7960b http://journal.frontiersin.org/Journal/10.3389/fendo.2016.00005/full |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....74f1c9f647f5cde726a434e582d7960b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16642392 |
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| DOI: | 10.3389/fendo.2016.00005/full |