Measuring the lactate-to-creatine ratio via 1 H NMR spectroscopy can be used to noninvasively evaluate apoptosis in glioma cells after X-ray irradiation

• Autorzy: Li H. , Cui Y. , Li F. , Shi W. , Gao W. , Wang X. , Zeng Q.
• Języki publikacji: EN

Abstrakty

EN

Background: Radiotherapy is among the commonly applied treatment options for glioma, which is one of the most common types of primary brain tumor. To evaluate the effect of radiotherapy noninvasively, it is vital for oncologists to monitor the effects of X-ray irradiation on glioma cells. Preliminary research had showed that PKC-ι expression correlates with tumor cell apoptosis induced by X-ray irradiation. It is also believed that the lactate-to-creatine (Lac/Cr) ratio can be used as a biomarker to evaluate apoptosis in glioma cells after X-ray irradiation. In this study, we evaluated the relationships between the Lac/Cr ratio, apoptotic rate, and protein kinase C iota (PKC-ι) expression in glioma cells. Methods: Cells of the glioma cell lines C6 and U251 were randomly divided into 4 groups, with every group exposed to X-ray irradiation at 0, 1, 5, 10 and 15 Gy. Single cell gel electrophoresis (SCGE) was conducted to evaluate the DNA damage. Flow cytometry was performed to measure the cell cycle blockage and apoptotic rates. Western blot analysis was used to detect the phosphorylated PKC-ι (p-PKC-ι) level. 1 H NMR spectroscopy was employed to determine the Lac/Cr ratio. Results: The DNA damage increased in a radiation dose-dependent manner (p < 0.05). With the increase in X-ray irradiation, the apoptotic rate also increased (C6, p < 0.01; U251, p < 0.05), and the p-PKC-ι level decreased (C6, p < 0.01; U251, p < 0.05). The p-PKC-ι level negatively correlated with apoptosis, whereas the Lac/Cr ratio positively correlated with the p-PKC-ι level. Conclusion: The Lac/Cr ratio decreases with an increase in X-ray irradiation and thus can be used as a biomarker to reflect the effects of X-ray irradiation in glioma cells.

• Wydawca: -
• Czasopismo: Cellular and Molecular Biology Letters
• Rocznik: 2018
• Tom: 23
• Opis fizyczny: p.1-11,fig.,ref.

Twórcy

autor

Li H.

• Department of Radiology, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan 250012, China

autor

Cui Y.

• Department of Radiology, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan 250012, China

autor

Li F.

• Department of Radiology, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan 250012, China

autor

Shi W.

• Department of Radiology, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan 250012, China

autor

Gao W.

• Department of Radiology, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan 250012, China

autor

Wang X.

• Department of Radiology, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan 250012, China

autor

Zeng Q.

• Department of Radiology, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan 250012, China

Bibliografia

• 1. Colen CB, Seraji-Bozorgzad N, Marples B, Galloway MP, Sloan AE, Mathupala SP. Metabolic remodeling of malignant gliomas for enhanced sensitization during radiotherapy: an in vitro study. Neurosurgery. 2006;59(6): 1313–23.
• 2. Li C, Li L, Xu C. Zhou J.Growth and radiosensitivity of irradiated human glioma cell progeny. NRR. 2008;3(5):542–5.
• 3. Annovazzi L, Caldera V, Mellai M, Riganti C, Battaglia L, Chirio D, Melcarne A, Schiffer D. The DNA damage/repair cascade in glioblastoma cell lines after chemotherapeutic agent treatment. Int J Oncol. 2015;46(6):2299–308.
• 4. Yang L, Yuan X, Wang J, Gu C, Zhang H, Yu J, Liu F. Radiosensitization of human glioma cells by tamoxifen is associated with the inhibition of PKC- activity in vitro. Oncol Lett. 2015;10(1):473–8.
• 5. do Carmo A, Balca-Silva J, Matias D, Lopes MC. PKC signaling in glioblastoma. Cancer Biol Ther. 2013;14(4):287–94.
• 6. Patel R, Win H, Desai S, Patel K, Matthews JA, Acevedo-Duncan M. Involvement of PKC-iota in glioma proliferation. Cell Prolif. 2008;41(1):122–35.
• 7. Martiny-Baron G, Fabbro D. Classical PKC isoforms in cancer. Pharmacol Res. 2007;55(6):477–86.
• 8. Jatoi A, Radecki Breitkopf C, Foster NR, Block MS, Grudem M, Wahner Hendrickson A, Carlson RE, Barrette B, Karlin N, Fields AP. A mixed-methods feasibility trial of protein kinase C iota inhibition with auranofin in asymptomatic ovarian cancer patients. Oncology. 2015;88(4):208–13.
• 9. Zhang Z, Zeng Q, Liu Y, Li C, Feng D, Wang J. Assessment of the intrinsic radiosensitivity of glioma cells and monitoring of metabolite ratio changes after irradiation by 14.7-T highresolution H-1 MRS. NMR Biomed. 2014; 27(5):547–52.
• 10. Bitomsky N, Conrad E, Moritz C, Polonio-Vallon T, Sombroek D, Schultheiss K, Glas C, Greiner V, Herbel C, Mantovani F, et al. Autophosphorylation and Pin1 binding coordinate DNA damage- induced HIPK2 activation and cell death. PNatl AcadSci USA. 2013;110(45):E4203–12.
• 11. Park S, Choi S, Ahn B. DNA strand breaks in mitotic germ cells of Caenorhabditis elegans evaluated by comet assay. Mol Cells. 2016;39(3):204–10.
• 12. Maachani UB, Kramp T, Hanson R, Zhao S, Celiku O, Shankavaram U, Colombo R, Caplen NJ, Camphausen K, Tandle A. Targeting MPS1 enhances Radiosensitization of human glioblastoma by modulating DNA repair proteins. Mol Cancer Res. 2015;13(5):852–62.
• 13. Q-q Z, W-j W, Li J, Yang N, Chen G, Wang Z, Z-q L. Cathepsin L suppression increases the radiosensitivity of human glioma U251 cells via G(2)/M cell cycle arrest and DNA damage. Acta Pharmacol Sin. 2015;36(9):1113–25.
• 14. Cerne JZ, Hartig SM, Hamilton MP, Chew SA, Mitsiades N, Poulaki V, McGuire SE. Protein kinase C inhibitors sensitize GNAQ mutant uveal melanoma cells to ionizing radiation. Invest Ophthalmol Vis Sci. 2014;55(4):2130–9.
• 15. Dou W, Zhang M, Zhang X, Li Y, Chen H, Li S, Lu M, Dai J, Constans JM. Convex-envelope based automated quantitative approach to multi-voxel 1H-MRS applied to brain tumor analysis. PLoS One. 2015;10(9):e0137850.
• 16. Zeng Q-S, Li C-F, Zhang K, Liu H, Kang X-S, Zhen J-H. Multivoxel 3D proton MR spectroscopy in the distinction of recurrent glioma from radiation injury. J Neuro-Oncol. 2007;84(1):63–9.
• 17. Kennedy KM, Scarbrough PM, Ribeiro A, Richardson R, Yuan H, Sonveaux P, Landon CD, Chi J-T, Pizzo S, Schroeder T, et al. Catabolism of exogenous lactate reveals it as a legitimate metabolic substrate in breast Cancer. PLoS One. 2013;8(9):e75154.
• 18. Balca-Silva J, Matias D, do Carmo A, Girao H, Moura-Neto V, Sarmento-Ribeiro AB, Lopes MC. Tamoxifen in combination with temozolomide induce a synergistic inhibition of PKC-pan in GBM cell lines. BBA-Gen Subjects. 2015;1850(4):722–32.
• 19. Dai H, Hong B, Xiao Y, Yang Y, Ma L, Chen Y. Wu R.Extraction methods optimization in high-field MRS study of the human umbilical cord mesenchymal stem cells. Chin. J Magn Reson Imaging. 2011;2(6):430–6.
• 20. Li H, Xu Y, Shi W, Li F, Zeng Q, Yi C. Assessment of alterations in X-ray irradiation-induced DNA damage of glioma cells by using proton nuclear magnetic resonance spectroscopy. Int J Biochem Cell Biol. 2017;22(84):109–18.
• 21. Kimura-Ohba S, Yang Y. Oxidative DNA damage mediated by Intranuclear MMP activity is associated with neuronal apoptosis in ischemic stroke. Oxidmedcell longev. 2016;2016:6927328–8.
• 22. Bussink J. Span PN.Gamma-H2AX foci in peripheral blood lymphocytes to quantify radiation-induced DNA damage after 177Lu-DOTA-octreotate peptide receptor radionuclide therapy. J Nucl Med. 2015;56(4):501–2.
• 23. X-y F, Zhang S, Wang K, M-f Y, C-d F, B-l S. Caudatin inhibits human glioma cells growth through triggering DNA damage-mediated cell cycle arrest. CellMolNeurobiol. 2015;35(7):953–9.
• 24. Kikuchi K, Soundararajan A, Zarzabal LA, Weems CR, Nelon LD, Hampton ST, Michalek JE, Rubin BP, Fields AP, Keller C. Protein kinase C iota as a therapeutic target in alveolar rhabdomyosarcoma. Oncogene. 2013;32(3):286–95.
• 25. Matoba S, Kang J-G, Patino WD, Wragg A, Boehm M, Gavrilova O, Hurley PJ, Bunz F. Hwang PM.p53 regulates mitochondrial respiration. Cardiovasc DrugTher. 2006;20(6):415–5.
• 26. Contractor T, Harris CR. p53 negatively regulates transcription of the pyruvate dehydrogenase kinase Pdk2. Cancer Res. 2012;72(2):560–7.
• 27. Martinez-Outschoorn UE, Sotgia F, Lisanti MP. Power surge: supporting cells "fuel" Cancer cell mitochondria. Cell Metab. 2012;15(1):4–5.28.
• 28. Martinez-Bisbal MC, Marti-Bonmati L, Piquer J, Revert A, Ferrer P, Llacer JL, Piotto M, Assemat O, Celda B. H-1 and C-13 HR-MAS spectroscopy of intact biopsy samples ex vivo and in vivo H-1 MRS study of human high grade gliomas. NMR Biomed. 2004;17(4):191–205.

Identyfikatory

DOI

10.1186/s11658-018-0092-2