Radiosensitization of normoxic and hypoxic h1339 lung tumor cells by heat shock protein 90 inhibition is independent of hypoxia inducible factor-1α.

PloS One
Daniela SchillingGabriele Multhoff

Abstract

Ionizing irradiation is a commonly accepted treatment modality for lung cancer patients. However, the clinical outcome is hampered by normal tissue toxicity and tumor hypoxia. Since tumors often have higher levels of active heat shock protein 90 (Hsp90) than normal tissues, targeting of Hsp90 might provide a promising strategy to sensitize tumors towards irradiation. Hsp90 client proteins include oncogenic signaling proteins, cell cycle activators, growth factor receptors and hypoxia inducible factor-1α (HIF-1α). Overexpression of HIF-1α is assumed to promote malignant transformation and tumor progression and thus might reduce the accessibility to radiotherapy. Herein, we describe the effects of the novel Hsp90 inhibitor NVP-AUY922 and 17-allylamino-17-demethoxygeldanamycin (17-AAG), as a control, on HIF-1α levels and radiosensitivity of lung carcinoma cells under normoxic and hypoxic conditions. NVP-AUY922 exhibited a similar biological activity to that of 17-AAG, but at only 1/10 of the dose. As expected, both inhibitors reduced basal and hypoxia-induced HIF-1α levels in EPLC-272H lung carcinoma cells. However, despite a down-regulation of HIF-1α upon Hsp90 inhibition, sensitivity towards irradiation remained unaltered in EPL...Continue Reading

References

Dec 12, 2000·The Journal of Biological Chemistry·L B GardnerC V Dang
Feb 13, 2001·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·N ChoiP Kosmidis
Jan 10, 2002·The Journal of Biological Chemistry·Dorthe M KatschinskiRoland H Wenger
Jun 8, 2002·The Journal of Biological Chemistry·Jennifer S IsaacsLeonard M Neckers
Jul 20, 2002·International Journal of Radiation Oncology, Biology, Physics·Michael I KoukourakisAdrian L Harris
Jul 27, 2002·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·Daniel M AebersoldValentin Djonov
Jul 16, 2004·Seminars in Radiation Oncology·Peter Vaupel
Aug 21, 2004·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Dörthe M KatschinskiRoland H Wenger
Sep 29, 2004·Journal of Clinical Pathology·A E Greijer, E van der Wall
Aug 16, 2005·Cancer Cell·Benjamin J MoellerMark W Dewhirst
Sep 1, 2005·The Journal of Biological Chemistry·Jinsong YangRichard K Bruick
Oct 6, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Udai BanerjiPaul Workman
Dec 3, 2005·Cancer Research·Nadia O IbrahimDörthe M Katschinski
Apr 19, 2007·Cancer Metastasis Reviews·Peter Vaupel, Arnulf Mayer
Aug 3, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Kevin Camphausen, Philip J Tofilon
Nov 21, 2007·Journal of Medicinal Chemistry·Paul A BroughLisa Wright
Mar 18, 2009·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Daniela SchillingGabriele Multhoff
Nov 26, 2009·Proceedings of the National Academy of Sciences of the United States of America·Elana S EhrlichXiao-Fang Yu
Dec 1, 2009·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Alexander E KabakovVladimir L Gabai
Mar 9, 2010·Experimental Cell Research·Junye LiuGuozhen Guo
May 12, 2010·Molecular Cancer Therapeutics·Nathalie GasparPaul Workman
May 12, 2010·The Journal of Clinical Investigation·Bart van de SluisEzra Burstein
Jul 24, 2010·Nature Reviews. Cancer·Jane TrepelLen Neckers
Feb 10, 2012·Strahlentherapie und Onkologie : Organ der Deutschen Röntgengesellschaft ... [et al]·D SchillingG Multhoff
Mar 24, 2012·Strahlentherapie und Onkologie : Organ der Deutschen Röntgengesellschaft ... [et al]·L StinglM Flentje

❮ Previous
Next ❯

Citations

Oct 12, 2012·Strahlentherapie und Onkologie : Organ der Deutschen Röntgengesellschaft ... [et al]·L HelbigD Zips
Feb 26, 2014·Expert Review of Proteomics·Sergej SkvortsovIra Skvortsova
Aug 30, 2014·Stem Cell Research·James A L BrownFrank Barry
Feb 28, 2015·Cancer Letters·Daniela SchillingGabriele Multhoff
Oct 21, 2015·Journal of Receptor and Signal Transduction Research·Shou-He LiaoHua-Fu Zhou
Jan 30, 2013·Cancer Biology & Therapy·Nishant GandhiPhuoc T Tran
Jun 16, 2019·Radiation and Environmental Biophysics·Daniela SchillingThomas E Schmid
Jul 25, 2021·Cancers·Julien AncelValérian Dormoy

❮ Previous
Next ❯

Methods Mentioned

BETA
ubiquitination
xenografts
ELISA
transfection
FCS
Protein Assay
Assay

Software Mentioned

SPSS
ImageJ
ModFit LT
Systat
Sigmaplot

Related Concepts

Related Feeds

Cancer Metabolism

In order for cancer cells to maintain rapid, uncontrolled cell proliferation, they must acquire a source of energy. Cancer cells acquire metabolic energy from their surrounding environment and utilize the host cell nutrients to do so. Here is the latest research on cancer metabolism.