Skip to main content
Log in

Sodium butyrate increases the effect of the photodynamic therapy: a mechanism that involves modulation of gene expression and differentiation in astrocytoma cells

  • Original Paper
  • Published:
Child's Nervous System Aims and scope Submit manuscript

Abstract

Objectives

In order to evaluate the improvement of the photodynamic therapy (PDT) due to sodium butyrate (NaBu), its effectiveness in U373-MG and D54-MG astrocytoma cell lines was evaluated.

Methods

Cells were exposed to delta-aminolevulinic acid (δ-ALA) as a precursor to endogenous photosensitizer protoporphyrin IX (PpIX). In both astrocytoma cells, an important increase by ALA was observed in uroporphyrinogen synthetase gene expression: 1.8- and 52-fold for D54-MG and U373-MG cells, respectively. After irradiation, they showed 16.67 and 28.9 % of mortality in U373-MG and D54-MG, respectively. These mortalities increased to 70.62 and 96.7 % when U373-MG and D54-MG cells, respectively, were exposed 24 h to 8 mM NaBu, before to PpIX induction. NaBu induced expression of caspase-3, caspase-9, and Bcl-2 and increased Bax in U373-MG cells. ALA-induced morphological changes are compatible to differentiation.

Conclusions

Genes and differentiation induced mainly by NaBu improve cell death performed by PDT in astrocytoma cells. These facts prove the synergistic effect of NaBu on cytotoxic damage induced by PDT.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Chico-Ponce de León F, Castro-Sierra E, Pérezpeña-Diazconti M, Gordillo-Domínguez LF, Santana-Montero BL, Rocha-Rivero LE, Vaca-Ruíz MA, Ríos-Alanís M, Sánchez-Herrera F, Valdéz-Orduño R (2006) Tumores intracraneanos del niño. Bol Med Hosp Infant Mex 63:367–381

    Google Scholar 

  2. Kleihues P, Ohgaki H (1999) Primary and secondary glioblastomas: from concept to clinical diagnosis. Neurooncology 1:44–51

    CAS  Google Scholar 

  3. Schmidt-Erfurth U, Diddens H, Birngruber R, Hasan T (1997) Photodynamic targeting of human retinoblastoma cells using covalent low-density lipoprotein conjugates. Br J Cancer 75:54–61

    Article  PubMed  CAS  Google Scholar 

  4. Kessel D, Woodburn K (1993) Biodistribution of photosensitizing agents. Int J Biochem 25:1377–1383

    Article  PubMed  CAS  Google Scholar 

  5. Oleinick NL, Morris RL, Belichenko I (2002) The role of apoptosis in response to photodynamic therapy: what, where, why and how. Photochem Photobiol Sci 1:1–21

    Article  PubMed  CAS  Google Scholar 

  6. Wu SM, Ren QG, Zhou MO, Peng Q, Chen JY (2003) Protopporphyrin IX production and its photodynamic effects on glioma cells, neuroblastoma cells and normal cerebellar granule cells in vitro with 5-aminolevulinic acid and its hexylester. Cancer Let 200:123–131

    Article  CAS  Google Scholar 

  7. Ruiz-Galindo E, Arenas-Huertero F, Ramón-Gallegos E (2007) Expression of genes involved in heme biosynthesis in the human retinoblastoma cell lines WERI-Rb-1 and Y79: implications for photodynamic therapy. J Exp Clin Cancer Res 26:195–200

    PubMed  CAS  Google Scholar 

  8. Olivo M, Wilson BC (2004) Mapping ALA-induced PPIX fluorescence in normal brain and brain tumour using confocal fluorescence microscopy. Int J Oncol 25:37–45

    PubMed  CAS  Google Scholar 

  9. Dailey HA, Smith A (1984) Differential interaction of porphyrins used in photoradiation therapy with ferrochelatase. Biochem J 223:441–445

    PubMed  CAS  Google Scholar 

  10. Wild PJ, Krieg RC, Seidl J et al (2005) RNA expression profiling of normal and tumor cells following photodynamic therapy with 5-aminolevulinic acid-induced protoporphyrin IX in vitro. Mol Cancer Ther 4:516–528

    Article  PubMed  CAS  Google Scholar 

  11. Urnov FD (2003) Chromatin remodeling as a guide to transcriptional regulatory networks in mammals. J Cell Biochem 88:684–694

    Article  PubMed  CAS  Google Scholar 

  12. Gore SD, Carducci MA (2000) Modifying histones to care cancer: clinical development of sodium phenylbutyrate and other histone deacetylase inhibitors. Expert Opin Invest Drugs 9:2923–2934

    Article  CAS  Google Scholar 

  13. Marks PA, Richon VM, Rifkind RA (2000) Histone deacetylase inhibitors: inducers of differentiation or apoptosis of transformed cells. J Natl Cancer Inst 92:1210–1216

    Article  PubMed  CAS  Google Scholar 

  14. Widmer J, Fassihi KS, Schlichter SC, Wheeler KS, Crute BE, King N, Nutile-McMenemy N, Noll WW, Daniel S, Ha J, Kim KH, Witters LA (1996) Identification of a second human acetyl-CoA carboxylase gene. Biochem J 316:915–922

    PubMed  CAS  Google Scholar 

  15. Wang J, Saunthararajah Y, Redner RL, Liu JM (1999) Inhibitors of histone deacetylase relieve ETO-mediated repression and induce differentiation of AML1-ETO leukemia cells. Cancer Res 59:2766–2769

    PubMed  CAS  Google Scholar 

  16. Butler LM, Agus DB, Scher HI, Higgins B, Rose A, Cordon-Cardo C, Thaler HT, Rifkind RA, Marks PA, Richon VM (2000) Suberoylanilide hydroxamic acid, an inhibitor of histone deacetylase, suppresses the growth of prostate cancer cells in vitro and in vivo. Cancer Res 60:5165–5170

    PubMed  CAS  Google Scholar 

  17. Piomelli SA (1973) Micromethod for free erythrocyte porphyrins: the FEP test. J Lab Clin Med 81:932–940

    PubMed  CAS  Google Scholar 

  18. Ramón-Gallegos E, DeLeón-Rodríguez I, Martínez-Guzmán LA, Pérez-Zapata AJ (1999) In vitro study of biosíntesis of protoporphyrin IX induced by δ-aminolevulinic acid in normal and cancerous cells of the human cervix. Arch Med Res 30:163–170

    Article  Google Scholar 

  19. Kennedy JC, Pottier RH, Pross DC (1990) Photodynamic therapy with endogenous protoporphyrin IX: basic principles and present clinical experience. J Photochem Photobiol 6:143–148

    Article  CAS  Google Scholar 

  20. Kemmner W, Wan K, Rüttinger S et al (2008) Silencing of human ferrochelatase causes abundant protoporphyrin-IX accumulation in colon cancer. FASEB J 22:500–509

    Article  PubMed  CAS  Google Scholar 

  21. Uzdensky A, Juzeniene A, Ma LW, Moan J (2004) Photodynamic inhibition of enzymatic detachment of human cancer cells from a substratum. Biochem Biophys Res Commun 322:452–457

    Article  PubMed  CAS  Google Scholar 

  22. Oltvai ZN, Milliman CL, Korsmeyer SJ (1993) Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 74:609–619

    Article  PubMed  CAS  Google Scholar 

  23. Neise D, Graupner V, Gillissen BF, Daniel PT, Schulze-Osthoff K, Janicke RU, Essmann F (2008) Activation of the mitochondrial death pathway is commonly mediated by a preferential engagement of Bak. Oncogene 27:1387–1396

    Article  PubMed  CAS  Google Scholar 

  24. Karmakar S, Banik NL, Patel SJ, Ray SK (2007) 5-Aminolevulinic acid-based photodynamic therapy suppressed survival factors and activated proteases for apoptosis in human glioblastoma U87MG cells. Neurosci Lett 415:242–247

    Article  PubMed  CAS  Google Scholar 

  25. Ortel B, Chen N, Brissette J, Dotto GP, Maytin E, Hasan T (1998) Differentiation-specific increase in ALA-induced protoporphyrin IX accumulation in primary mouse keratinocytes. Br J Cancer 77:1744–1751

    Article  PubMed  CAS  Google Scholar 

  26. Appelskog IB, Ammerpohl O, Svechnikova IG, Lui WO, Almqvist PM, Ekström TJ (2004) Histone deacetylase inhibitor 4-phenylbutyrate suppresses GAPDH mRNA expression in glioma cells. Int J Oncol 24:1419–1425

    PubMed  CAS  Google Scholar 

  27. Flores-Ancona RM, Garcia-Gomez FY, Jimenez-Betanzos AM, Solis-Paredes M, Castro-Leyva V, Cruz-Orea A, Arenas-Huertero F, Ramon-Gallegos E (2009) Effects of sodium butyrate on cell death induced by photodynamic therapy in U373-MG and D54-MG astrocytoma cell lines. Photochem Photobiol 85:1182–1188

    Article  PubMed  CAS  Google Scholar 

  28. Li X-N, Shu Q, Su JM-F, Perlaky L, Blaney SM, Lau Ch C (2005) Valproic acid induces growth arrest, apoptosis, and senescence in medulloblastomas by increasing histone hyperacetylation and regulating expression of p21Cip1, CDK4, and CMYC. Mol Cancer Ther 4:1921–1922

    Google Scholar 

Download references

Acknowledgments

Financing for this study was provided by Sistema de Investigación y Posgrado through project 20070480 under the direction of Eva Ramon-Gallegos. ERG is Sistema Nacional de Investigadores (SNI), Comisión Operadora para el Fomentos a las Actividades Académicas and Estímulo al Desarrollo de la Investigación fellow. F A-H is a member of the Sistema Nacional de Investigadores (SNI-I).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Francisco Arenas-Huertero.

Additional information

José Bueno-Carrazco, Violeta Castro-Leyva, Fanny García-Gomez, and Mario Solís-Paredes contributed equally in the paper.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bueno-Carrazco, J., Castro-Leyva, V., García-Gomez, F. et al. Sodium butyrate increases the effect of the photodynamic therapy: a mechanism that involves modulation of gene expression and differentiation in astrocytoma cells. Childs Nerv Syst 28, 1723–1730 (2012). https://doi.org/10.1007/s00381-012-1828-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00381-012-1828-3

Keywords

Navigation