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Combined effects of resveratrol and radiation in GH3 and TtT/GF pituitary adenoma cells

  • Laboratory Investigation
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Objective

Resveratrol and radiation decrease viability in various tumor cells. This study aims to investigate combined effects of resveratrol and radiation on viability, induction of apoptosis and necrosis, and expression of apoptosis modulators in rodent GH3 and TtT/GF pituitary adenoma cells in vitro.

Methods

Cells were incubated with 10–100 µM resveratrol. Medium and medium with ethanol served as controls. After 2 h, cells were irradiated with 0–5 Gray (Gy) and further incubated for 48–72 h. Cell viability was quantified using a hemocytometer. Cell death was assessed with an enzyme-linked immunosorbent assay (ELISA) that detects free nucleosomes in cell lysates and free nucleosomes released to the culture medium. Expression of B-cell lymphoma-2 protein (BCL-2) and BCL-2 associated Xprotein (BAX) was measured using quantitative real time-polymerase chain reaction (qRT-PCR) to analyze changes in BAX/BCL-2 ratio.

Results

Resveratrol and irradiation with 4 Gy alone and in combination significantly decreased cell viability (p = 0.017 and less). In the ELISA, 10 μM resveratrol significantly induced apoptosis in TtT/GF cells at 0 Gy (p < 0.001), but not at 3 or 5 Gy. In the ELISA, 10 μM resveratrol significantly induced necrosis in GH3 cells at 0, 3 and 5 Gy (p < 0.001). While qRT-PCR did not demonstrate a significant effect of 10 µM resveratrol or radiation on expression of BAX or BCL-2, a significant increase in the BAX/BCL-2 ratio was found after irradiation with 5 Gy in GH3 cells (p = 0.0027).

Conclusion

While moderate irradiation solely led to inhibited proliferation, resveratrol induced cell death in rodent pituitary adenoma cells.

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References

  1. Fahlbusch R, Buchfelder M (2011) Pituitary surgery. In: Melmed S (ed) The pituitary, 3rd edn. Academic Press, London, pp 703–719

    Chapter  Google Scholar 

  2. Athar M, Back JH, Kopelovich L, Bizkers DR, Kim AL (2009) Multiple molecular targets of resveratrol: anti-carcinogenic mechanisms. Arch Biochem Biophys 486:95–102

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Wang C, Hu ZQ, Chu M et al (2012) Resveratrol inhibited GH3 cell growth and decreased prolactin level via estrogen receptors. Clin Neurol Neurosurg 114:241–248

    Article  PubMed  Google Scholar 

  4. Zini R, Morin C, Bertelli A, Bertelli AA, Tillement JP (1999) Effects of resveratrol on the rat brain respiratory chain. Drugs Exp Clin Res 25(2-3):87–97

    PubMed  CAS  Google Scholar 

  5. Voellger B, Kirches E, Wilisch-Neumann A et al (2013) Resveratrol decreases B-cell lymphoma-2 expression and viability in GH3 pituitary adenoma cells of the rat. OncoTargets Ther 6:1269–1276

    Article  CAS  Google Scholar 

  6. Zhang X, Xu W, Su J, Chu M, Jin H, Li G, Tan C, Wang X, Wang C (2014) The prosurvival role of autophagy in resveratrol-induced cytotoxicity in GH3 cells. Int J Mol Med 33(4):987–993

    Article  PubMed  CAS  Google Scholar 

  7. Jeng YJ, Kochukov MY, Watson CS (2009). Membrane estrogen receptor-alpha-mediated nongenomic actions of phytoestrogens in GH3/B6/F10 pituitary tumor cells. J Mol Signal. https://doi.org/10.1186/1750-2187-4-2

    Article  PubMed  PubMed Central  Google Scholar 

  8. McCormack AI, Wass JA, Grossman AB (2011) Aggressive pituitary tumours: the role of temozolomide and the assessment of MGMT status. Eur J Clin Invest 41(10):1133–1148

    Article  PubMed  CAS  Google Scholar 

  9. Chomczynski P, Sacchi N (1987) Single-step method of RNA-isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162:156–159

    Article  PubMed  CAS  Google Scholar 

  10. Peña-Blanco A, García-Sáez AJ (2018) Bax, Bak and beyond—mitochondrial performance in apoptosis. FEBS J 285:416–431

    Article  PubMed  CAS  Google Scholar 

  11. Birkinshaw RW, Czabotar PE (2017) The BCL-2 family of proteins and mitochondrial outer membrane permeabilisation. Semin Cell Dev Biol 72:152–162

    Article  PubMed  CAS  Google Scholar 

  12. Yan WJ, Liu RB, Wang LK et al (2018) Sirt3-mediated autophagy contributes to resveratrol-induced protection against ER stress in HT22 cells. Front Neurosci. https://doi.org/10.3389/fnins.2018.00116

    Article  PubMed  PubMed Central  Google Scholar 

  13. Zhang Z, Liu Z, Chen J, Yi J, Cheng J, Dun W, Wei H (2018) Resveratrol induces autophagic apoptosis via the lysosomal cathepsin D pathway in human drug-resistant K562/ADM leukemia cells. Exp Ther Med 15:3012–3019

    PubMed  PubMed Central  Google Scholar 

  14. Kung HJ, Changou CA, Li CF, Ann DK (2015) Chromatophagy: autophagy goes nuclear and captures broken chromatin during arginine-starvation. Autophagy 11:419–421

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Chao W, Xuexin Z, Jun S, Ming C, Hua J, Li G, Tan C, Xu W (2014) Effects of resveratrol on cell growth and prolactin synthesis in GH3 cells. Exp Ther Med 7(4):923–928

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Jones MK, Padilla OR, Webb NA, Norng M (2008) The anti-apoptosis protein, survivin, mediates gastric epithelial cell cytoprotection against ethanol-induced injury via activation of the p34cdc2 cyclin-dependent kinase. J Cell Physiol 215:750–764

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Jones MK, Padilla OR, Zhu E (2010) Survivin is a key factor in the differential susceptibility of gastric endothelial and epithelial cells to alcohol-induced injury. J Physiol Pharmacol 61:253–264

    PubMed  PubMed Central  CAS  Google Scholar 

  18. Jie Q, Tang Y, Deng Y et al (2013) Bilirubin participates in protecting of heme oxygenase-1 induction by quercetin against ethanol hepatotoxicity in cultured rat hepatocytes. Alcohol 47(2):141–148

    Article  PubMed  CAS  Google Scholar 

  19. Lee SY, Ahn BT, Balk SH, Lee BL (1998) Tamoxifen inhibits GH3 cell growth in culture via enhancement of apoptosis. Neurosurgery 43(1):116–123

    Article  PubMed  CAS  Google Scholar 

  20. Cao L, Gao H, Gui S, Bai G, Lu R, Wang F, Zhang Y (2014) Effects of the estrogen receptor antagonist fulvestrant on F344 rat prolactinoma models. J Neurooncol 116(3):523–531

    Article  PubMed  CAS  Google Scholar 

  21. Walle T (2011) Bioavailability of resveratrol. Ann NY Acad Sci 1215:9–15

    Article  PubMed  CAS  Google Scholar 

  22. Walle T, Hsieh F, DeLegge MH et al (2004) High absorption but very low bioavailability of oral resveratrol in humans. Drug Metab Dispos 32:1377–1382

    Article  PubMed  CAS  Google Scholar 

  23. Mattarei A, Azzolini M, La Spina M, Zoratti M, Paradisi C, Biasutto L (2015) Amino acid carbamates as prodrugs of resveratrol. Sci Rep 5:15216

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Mattarei A, Carraro M, Azzolini M et al (2014) New water-soluble carbamate ester derivatives of resveratrol. Molecules 19(10):15900–15917

    Article  PubMed  CAS  Google Scholar 

  25. Gupta SC, Kannappan R, Reuter S, Kim JH, Aggarwal BB (2011) Chemosensitization of tumors by resveratrol. Ann NY Acad Sci 1215:150–160

    Article  PubMed  CAS  Google Scholar 

  26. Huang H, Lin H, Zhang X, Li J (2012) Resveratrol reverses temozolomide resistance by downregulation of MGMT in T98G glioblastoma cells by the NF-κB-dependent pathway. Oncol Rep 27:2050–2056

    Article  PubMed  CAS  Google Scholar 

  27. Tak JK, Lee JH, Park JW (2012) Resveratrol and piperine enhance radiosensitivity of tumor cells. BMB Rep 45:242–246

    Article  PubMed  CAS  Google Scholar 

  28. Fang Y, DeMarco VG, Nicholl MB (2012) Resveratrol enhances radiation sensitivity in prostate cancer by inhibiting cell proliferation and promoting cell senescence and apoptosis. Cancer Sci 103:1090–1098

    Article  PubMed  CAS  Google Scholar 

  29. Zhou JH, Cheng HY, Yu ZQ et al (2011) Resveratrol induces apoptosis in pancreatic cancer cells. Chin Med J 124:1695–1699

    PubMed  CAS  Google Scholar 

  30. Lin X, Wu G, Huo WQ, Zhang Y, Jin FS (2012) Resveratrol induces apoptosis associated with mitochondrial dysfunction in bladder carcinoma cells. Int J Urol 19:757–764

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

Dr. med. Jorge Humberto Tapia-Perez gave valuable technical advice.

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Authors and Affiliations

  1. Universitaetsklinik fuer Neurochirurgie, University Magdeburg, Magdeburg, Germany

    B. Voellger, Rosita Rupa, O. Melhem & R. Firsching

  2. Department of Neurosurgery, University Hospital of Marburg, Baldingerstr., 35033, Marburg, Germany

    B. Voellger & Rosita Rupa

  3. Department of Neuropathology, University Magdeburg, Magdeburg, Germany

    N. Waldt, E. Kirches & C. Mawrin

  4. Department of Radiation Therapy, University Magdeburg, Magdeburg, Germany

    H.-J. Ochel

Authors
  1. B. Voellger
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  2. N. Waldt
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  3. Rosita Rupa
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  4. E. Kirches
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  5. O. Melhem
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  6. H.-J. Ochel
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  7. C. Mawrin
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  8. R. Firsching
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Contributions

BV and EK conceived the project. BV, NW and OM carried out the experiments. BV, RR and EK wrote the manuscript. EK provided scientific counseling to the junior authors. RF and BV gave financial and administrative support. CM and H-JO provided laboratory facilities and staff. All authors read and approved the manuscript.

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Correspondence to B. Voellger.

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Voellger, B., Waldt, N., Rupa, R. et al. Combined effects of resveratrol and radiation in GH3 and TtT/GF pituitary adenoma cells. J Neurooncol 139, 573–582 (2018). https://doi.org/10.1007/s11060-018-2918-1

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  • DOI: https://doi.org/10.1007/s11060-018-2918-1

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