Effects of β-hydroxybutyrate on the proliferation and glycolysis in glioma cells

doi:10.3969/j.issn.1006-7795.2019.02.006

Abstract

Abstract: Objective To investigate the effects of β-hydroxybutyrate (β-HB), one of the ketogenic diet (KD) metabolites, on the proliferation and glycolysis of glioma cell lines to reveal the mechanisms of KD in the treatment of glioma. Methods After treated with different concentrations of β-HB, the proliferation of glioma cell lines U87 and LN229 was detected with CCK8 assay and glycolysis ability of cells was measured with glycolysis stress test. Further, the transcription factor c-myc expression was detected with Western blotting and real-time quantitative polymerase chain reaction (RT-qPCR). Results β-HB can inhibit the proliferation of glioma cells in a dose-dependent manner. Compared with the untreated group, the glycolysis level and maximum glycolytic capacity was decreased and the expression of c-myc was down-regulated in the experimental groups. Conclusion β-HB can affect the glycolytic capacity of glioma cell lines U87 and LN229 through c-myc, and thus inhibit cell growth. It is suggested that KD can be used as an efficacious therapy agent for glioma.

Key words: glioma, β-hydroxybutyrate, ketogenic diet, glycolysis

CLC Number:

R739.41

Yu Chunna, Jiang Bo, Li Wenbin, Chen Feng. Effects of β-hydroxybutyrate on the proliferation and glycolysis in glioma cells[J]. Journal of Capital Medical University, 2019, 40(2): 186-190.

0
/ / Recommend

Add to citation manager EndNote|Reference Manager|ProCite|BibTeX|RefWorks

URL: https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/10.3969/j.issn.1006-7795.2019.02.006

https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/Y2019/V40/I2/186

References

[1] Olar A, Aldape K D. Using the molecular classification of glioblastoma to in form personalized treatment[J]. J Pathol, 2013, 232(2):165-177.
[2] Seyfried T N, Shelton L M, Mukherjee P. Does the existing standard of care increase glioblastoma energy metabolism?[J]. Lancet Oncol, 2010, 11(9):809-811.
[3] Liberti M V, Locasale J W. Correction to:'the warburg effect:how does it benefit cancer cells?[J]. Trends Biochem Sci, 2016, 41(3):211-218.
[4] Caraballo R H, Flesler S, Armeno M, et al. Ketogenic diet in pediatric patients with refractory focal status epilepticus[J]. Epilepsy Res, 2014, 108(10):1912-1916.
[5] Youm Y H, Nguyen K Y, Grant R W, et al. Ketone body β-hydroxybutyrate blocks the NLRP3 inflammasome-mediated inflammatory disease[J]. Nat Med, 2015, 21(3):263-269.
[6] Lussier D M, Woolf E C, Johnson J L, et al. Enhanced immunity in a mouse model of malignant glioma is mediated by a therapeutic ketogenic diet[J]. BMC Cancer, 2016, 16(1):310.
[7] Nebeling L C, Miraldi F, Shurin S B, et al. Effects of a ketogenic diet on tumor metabolism and nutritional status in pediatric oncology patients:two case reports[J]. J Am Coll Nutr, 1995, 14(2):202-208.
[8] Zuccoli G, Marcello N, Pisanello A, et al. Metabolic management of glioblastoma multiforme using standard therapy with a restricted ketogenic diet:case report[J]. Nutr Metab (Lond),2010,7:33.
[9] Abdelwahab M G, Fenton K E, Preul M C, et al. The ketogenic diet is an effective adjuvant to radiation therapy for the treatment of malignant glioma[J]. PLoS One, 2012, 7(5):e36197.
[10] Lavanya B A, Caroline D R. β-Hydroxybutyrate in the brain:one molecule, multiple mechanisms[J]. Neurochem Res, 2017, 42(1):1-15.
[11] Woolf E C, Syed N, Scheck A C. Tumor metabolism, the ketogenic diet and β-hydroxybutyrate:novel approaches to adjuvant brain tumor therapy[J]. Front Mol Neurosci, 2016, 9:122.
[12] Newman J C, Verdin E. β-hydroxybutyrate:much more than a metabolite[J]. Diabetes Res Clin Pract, 2014, 106(2):173-181.
[13] Ganapathykanniappan S, Geschwind J F. Tumor glycolysis as a target for cancer therapy:progress and prospects[J]. Mol Cancer, 2013, 12(1):152.
[14] Newman J C, Verdin E. Ketone bodies as signaling metabolites[J]. Trends Endocrinol Metab, 2014, 25(1):42-52.
[15] Shukla S K, Gebregiworgis T, Purohit V, et al. Metabolic reprogramming induced by ketone bodies diminishes pancreatic cancer cachexia[J]. Cancer Metab, 2014, 2(1):18-18.
[16] Dang C V, Le A, Ping G. MYC-induced cancer cell energy metabolism and therapeutic opportunities[J]. Clin Cancer Res, 2009, 15(21):6479-6483.
[17] Dejure F R, Eilers M. MYC and tumor metabolism:chicken and egg[J]. EMBO J, 2017, 36(23):3409.
[18] 黄婷, 李军,卢驰,等.脑胶质瘤组织RRM1表达临床意义[J].中华肿瘤防治杂志,2018,25(6):394-401.