Radiotherapy & Oncology
Volume 92, Issue 3 , Pages 334-338 , September 2009

2-Methoxyestradiol-induced radiosensitization is independent of SOD but depends on inhibition of Akt and DNA-PKcs activities

  • Urszula Florczak

      Affiliations

    • Department of Radiation Oncology, University of Tuebingen, Germany
    • These authors shared the first authorship of this paper.
    • ,
  • Mahmoud Toulany

      Affiliations

    • Department of Radiation Oncology, University of Tuebingen, Germany
    • These authors shared the first authorship of this paper.
    • ,
  • Rainer Kehlbach

      Affiliations

    • Department of Diagnostic and Interventional Radiology, University of Tuebingen, Germany
    • ,
  • H. Peter Rodemann

      Affiliations

    • Department of Radiation Oncology, University of Tuebingen, Germany
    • Corresponding Author InformationCorresponding author. Address: Division of Radiobiology and Molecular Environmental Research, Department of Radiation Oncology, Eberhard-Karls University Tuebingen, Roentgenweg 11, 72076 Tuebingen, Germany.

Received 24 April 2009 ,Revised 2 June 2009 ,Accepted 5 June 2009.

References 

  1. Kamat JP, Boloor KK, Devasagayam TP, Jayashree B, Kesavan PC. Differential modification by caffeine of oxygen-dependent and independent effects of gamma-irradiation on rat liver mitochondria. Int J Radiat Biol. 2000;76:1281–1288
  2. Schmidt-Ullrich RK, Dent P, Grant S, Mikkelsen RB, Valerie K. Signal transduction and cellular radiation responses. Radiat Res. 2000;153:245–257
  3. Hirose Y, Mokuno K, Wakai M, et al. Elevated cerebrospinal fluid levels of manganese superoxide dismutase in bacterial meningitis. J Neurol Sci. 1995;131:51–57
  4. Motoori S, Majima HJ, Ebara M, et al. Overexpression of mitochondrial manganese superoxide dismutase protects against radiation-induced cell death in the human hepatocellular carcinoma cell line HLE. Cancer Res. 2001;61:5382–5388
  5. Huang P, Feng L, Oldham EA, Keating MJ, Plunkett W. Superoxide dismutase as a target for the selective killing of cancer cells. Nature. 2000;407:390–395
  6. Lin HL, Yang MH, Wu CW, et al. 2-Methoxyestradiol attenuates phosphatidylinositol 3-kinase/Akt pathway-mediated metastasis of gastric cancer. Int J Cancer. 2007;121:2547–2555
  7. LaVallee TM, Zhan XH, Herbstritt CJ, Kough EC, Green SJ, Pribluda VS. 2-Methoxyestradiol inhibits proliferation and induces apoptosis independently of estrogen receptors alpha and beta. Cancer Res. 2002;62:3691–3697
  8. Huober JB, Nakamura S, Meyn R, Roth JA, Mukhopadhyay T. Oral administration of an estrogen metabolite-induced potentiation of radiation antitumor effects in presence of wild-type p53 in non-small-cell lung cancer. Int J Radiat Oncol Biol Phys. 2000;48:1127–1137
  9. Zou H, Adachi M, Imai K, et al. 2-methoxyestradiol, an endogenous mammalian metabolite, radiosensitizes colon carcinoma cells through c-Jun NH2-terminal kinase activation. Clin Cancer Res. 2006;12:6532–6539
  10. Zou H, Zhao S, Zhang J, et al. Enhanced radiation-induced cytotoxic effect by 2-ME in glioma cells is mediated by induction of cell cycle arrest and DNA damage via activation of ATM pathways. Brain Res. 2007;1185:231–238
  11. Barchiesi F, Jackson EK, Fingerle J, Gillespie DG, Odermatt B, Dubey RK. 2-Methoxyestradiol, an estradiol metabolite, inhibits neointima formation and smooth muscle cell growth via double blockade of the cell cycle. Circ Res. 2006;99:266–274
  12. Kim TJ, Lee JW, Song SY, et al. Increased expression of pAKT is associated with radiation resistance in cervical cancer. Br J Cancer. 2006;94:1678–1682
  13. Tokunaga E, Kataoka A, Kimura Y, et al. The association between Akt activation and resistance to hormone therapy in metastatic breast cancer. Eur J Cancer. 2006;42:629–635
  14. Xing D, Orsulic S. A genetically defined mouse ovarian carcinoma model for the molecular characterization of pathway-targeted therapy and tumor resistance. Proc Natl Acad Sci USA. 2005;102:6936–6941
  15. Baumann M, Krause M, Dikomey E, et al. EGFR-targeted anti-cancer drugs in radiotherapy: preclinical evaluation of mechanisms. Radiother Oncol. 2007;83:238–248
  16. Corvo R. Evidence-based radiation oncology in head and neck squamous cell carcinoma. Radiother Oncol. 2007;85:156–170
  17. Dittmann K, Mayer C, Kehlbach R, Rodemann HP. The radioprotector Bowman–Birk proteinase inhibitor stimulates DNA repair via epidermal growth factor receptor phosphorylation and nuclear transport. Radiother Oncol. 2008;86:375–382
  18. Dittmann K, Mayer C, Wanner G, Kehlbach R, Rodemann HP. The radioprotector O-phospho-tyrosine stimulates DNA-repair via epidermal growth factor receptor- and DNA-dependent kinase phosphorylation. Radiother Oncol. 2007;84:328–334
  19. Kim IA, No M, Lee JM, et al. Epigenetic modulation of radiation response in human cancer cells with activated EGFR or HER-2 signaling: potential role of histone deacetylase 6. Radiother Oncol. 2009;92:125–132
  20. Krause M, Prager J, Zhou X, et al. EGFR-TK inhibition before radiotherapy reduces tumour volume but does not improve local control: differential response of cancer stem cells and nontumourigenic cells?. Radiother Oncol. 2007;83:316–325
  21. Weppler SA, Li Y, Dubois L, et al. Expression of EGFR variant vIII promotes both radiation resistance and hypoxia tolerance. Radiother Oncol. 2007;83:333–339
  22. Bussink J, Kaanders JH, van der Kogel AJ. Microenvironmental transformations by VEGF- and EGF-receptor inhibition and potential implications for responsiveness to radiotherapy. Radiother Oncol. 2007;82:10–17
  23. Toulany M, Dittmann K, Fehrenbacher B, Schaller M, Baumann M, Rodemann HP. PI3K-Akt signaling regulates basal, but MAP-kinase signaling regulates radiation-induced XRCC1 expression in human tumor cells in vitro. DNA Repair (Amst). 2008;7:1746–1756
  24. Kao GD, Jiang Z, Fernandes AM, Gupta AK, Maity A. Inhibition of phosphatidylinositol-3-OH kinase/Akt signaling impairs DNA repair in glioblastoma cells following ionizing radiation. J Biol Chem. 2007;282:21206–21212
  25. Golding SE, Morgan RN, Adams BR, Hawkins AJ, Povirk LF, Valerie K. Pro-survival AKT and ERK signaling from EGFR and mutant EGFRvIII enhances DNA double-strand break repair in human glioma cells. Cancer Biol Ther. 2009;8:730–738
  26. Toulany M, Kasten-Pisula U, Brammer I, et al. Blockage of epidermal growth factor receptor-phosphatidylinositol 3-kinase-AKT signaling increases radiosensitivity of K-RAS mutated human tumor cells in vitro by affecting DNA repair. Clin Cancer Res. 2006;12:4119–4126
  27. Toulany M, Kehlbach R, Florczak U, et al. Targeting of AKT1 enhances radiation toxicity of human tumor cells by inhibiting DNA-PKcs-dependent DNA double-strand break repair. Mol Cancer Ther. 2008;7:1772–1781
  28. Toulany M, Dittmann K, Baumann M, Rodemann HP. Radiosensitization of Ras-mutated human tumor cells in vitro by the specific EGF receptor antagonist BIBX1382BS. Radiother Oncol. 2005;74:117–129
  29. Toulany M, Dittmann K, Kruger M, Baumann M, Rodemann HP. Radioresistance of K-Ras mutated human tumor cells is mediated through EGFR-dependent activation of PI3K-AKT pathway. Radiother Oncol. 2005;76:143–150
  30. Kachadourian R, Liochev SI, Cabelli DE, Patel MN, Fridovich I, Day BJ. 2-Methoxyestradiol does not inhibit superoxide dismutase. Arch Biochem Biophys. 2001;392:349–353
  31. Veldwijk MR, Herskind C, Laufs S, Zeller WJ, Fruehauf S, Wenz F. Recombinant adeno-associated virus 2-mediated transfer of the human superoxide-dismutase gene does not confer radioresistance on HeLa cervical carcinoma cells. Radiother Oncol. 2004;72:341–350

PII: S0167-8140(09)00317-X

doi: 10.1016/j.radonc.2009.06.005

Radiotherapy & Oncology
Volume 92, Issue 3 , Pages 334-338 , September 2009

Article Tools

* Image Usage & Resolution