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Beta-hydroxybutyrate (3-OHB) can influence the energetic phenotype of breast cancer cells, but does not impact their proliferation and the response to chemotherapy or radiation.

التفاصيل البيبلوغرافية
العنوان: Beta-hydroxybutyrate (3-OHB) can influence the energetic phenotype of breast cancer cells, but does not impact their proliferation and the response to chemotherapy or radiation.
المؤلفون: Bartmann C; 1Department of Obstetrics and Gynaecology, University Hospital of Würzburg, Josef-Schneider-Str. 4, 97080 Würzburg, Germany., Janaki Raman SR; 2Department of Biochemistry and Molecular Biology, Theodor-Boveri-Institute, Biocenter, University of Würzburg, 97070 Würzburg, Germany., Flöter J; 2Department of Biochemistry and Molecular Biology, Theodor-Boveri-Institute, Biocenter, University of Würzburg, 97070 Würzburg, Germany., Schulze A; 2Department of Biochemistry and Molecular Biology, Theodor-Boveri-Institute, Biocenter, University of Würzburg, 97070 Würzburg, Germany., Bahlke K; 1Department of Obstetrics and Gynaecology, University Hospital of Würzburg, Josef-Schneider-Str. 4, 97080 Würzburg, Germany., Willingstorfer J; 1Department of Obstetrics and Gynaecology, University Hospital of Würzburg, Josef-Schneider-Str. 4, 97080 Würzburg, Germany., Strunz M; 1Department of Obstetrics and Gynaecology, University Hospital of Würzburg, Josef-Schneider-Str. 4, 97080 Würzburg, Germany., Wöckel A; 1Department of Obstetrics and Gynaecology, University Hospital of Würzburg, Josef-Schneider-Str. 4, 97080 Würzburg, Germany., Klement RJ; 3Department of Radiotherapy and Radiation Oncology, Leopoldina Hospital, 97422 Schweinfurt, Germany., Kapp M; 1Department of Obstetrics and Gynaecology, University Hospital of Würzburg, Josef-Schneider-Str. 4, 97080 Würzburg, Germany., Djuzenova CS; 4Department of Radiotherapy, University Hospital of Würzburg, 97080 Würzburg, Germany., Otto C; 5Experimental Surgery, Department of General, Visceral, Vascular, and Pediatric Surgery, University Hospital of Würzburg, 97080 Würzburg, Germany., Kämmerer U; 1Department of Obstetrics and Gynaecology, University Hospital of Würzburg, Josef-Schneider-Str. 4, 97080 Würzburg, Germany.
المصدر: Cancer & metabolism [Cancer Metab] 2018 Jun 11; Vol. 6, pp. 8. Date of Electronic Publication: 2018 Jun 11 (Print Publication: 2018).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: BioMed Central Country of Publication: England NLM ID: 101607582 Publication Model: eCollection Cited Medium: Print ISSN: 2049-3002 (Print) Linking ISSN: 20493002 NLM ISO Abbreviation: Cancer Metab Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: London : BioMed Central, 2013-
مستخلص: Background: Ketogenic diets (KDs) or short-term fasting are popular trends amongst supportive approaches for cancer patients. Beta-hydroxybutyrate (3-OHB) is the main physiological ketone body, whose concentration can reach plasma levels of 2-6 mM during KDs or fasting. The impact of 3-OHB on the biology of tumor cells described so far is contradictory. Therefore, we investigated the effect of a physiological concentration of 3 mM 3-OHB on metabolism, proliferation, and viability of breast cancer (BC) cells in vitro.
Methods: Seven different human BC cell lines (BT20, BT474, HBL100, MCF-7, MDA-MB 231, MDA-MB 468, and T47D) were cultured in medium with 5 mM glucose in the presence of 3 mM 3-OHB at mild hypoxia (5% oxygen) or normoxia (21% oxygen). Metabolic profiling was performed by quantification of the turnover of glucose, lactate, and 3-OHB and by Seahorse metabolic flux analysis. Expression of key enzymes of ketolysis as well as the main monocarboxylic acid transporter MCT2 and the glucose-transporter GLUT1 was analyzed by RT-qPCR and Western blotting. The effect of 3-OHB on short- and long-term cell proliferation as well as chemo- and radiosensitivity were also analyzed.
Results: 3-OHB significantly changed the oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) in BT20 cells resulting in a more oxidative energetic phenotype. MCF-7 and MDA-MB 468 cells had increased ECAR only in response to 3-OHB, while the other three cell types remained uninfluenced. All cells expressed MCT2 and GLUT1, thus being able to uptake the metabolites. The consumption of 3-OHB was not strongly linked to mRNA overexpression of key enzymes of ketolysis and did not correlate with lactate production and glucose consumption. Neither 3-OHB nor acetoacetate did interfere with proliferation. Further, 3-OHB incubation did not modify the response of the tested BC cell lines to chemotherapy or radiation.
Conclusions: We found that a physiological level of 3-OHB can change the energetic profile of some BC cell lines. However, 3-OHB failed to influence different biologic processes in these cells, e.g., cell proliferation and the response to common breast cancer chemotherapy and radiotherapy. Thus, we have no evidence that 3-OHB generally influences the biology of breast cancer cells in vitro.
Competing Interests: Not applicableThe authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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فهرسة مساهمة: Keywords: Breast cancer; Chemotherapy; Ionizing radiation; Ketogenic diet; Ketone bodies; Metabolic profile; Seahorse; β-Hydroxybutyrate
تواريخ الأحداث: Date Created: 20180627 Latest Revision: 20220318
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC5996481
DOI: 10.1186/s40170-018-0180-9
PMID: 29942509
قاعدة البيانات: MEDLINE
الوصف
تدمد:2049-3002
DOI:10.1186/s40170-018-0180-9