PMID: 15360086Sep 14, 2004Paper

Radicicol potentiates heat-induced cell killing in a human oesophageal cancer cell line: the Hsp90 chaperone complex as a new molecular target for enhancement of thermosensitivity

International Journal of Radiation Biology
T AkimotoN Mitsuhashi

Abstract

To examine the ability of a heat shock protein 90 (Hsp90) chaperone complex inhibitor, radicicol, to modify thermal response and heat-induced cell killing, and to clarify the underlining mechanisms. A human oesophageal cancer cell line (TE-1), with a mutant p53 gene, was used. To examine the effect of radicicol on heat-induced cell killing, radicicol at a concentration of 100 nM was incubated with the cells for 7 h during heat treatment. Changes in the expression of proteins were examined by Western blot and immunofluorescence analysis. Radicicol in combination with heat synergistically potentiated heat-induced cellular killing despite an increase in the expression of Hsp72 and Hsp27 caused by radicicol. Heat alone activated Raf-1 and p42/p44 extracellular signal-regulated kinase (Erk), and heat in combination with radicicol inhibited the activation of Raf-1 and p42/p44 Erk through reduced binding of Raf-1 to Hsp90. Phosphorylation of Akt was also decreased by radicicol. The Hsp90 chaperone complex inhibitor, radicicol, potentiated heat-induced cellular killing, and inhibition of p42/p44 Erk and Akt activation rather than modification of Hsp expression might be involved in enhancing cellular thermosensitivity. Results suggest t...Continue Reading

References

Jul 18, 1997·The Journal of Biological Chemistry·V L GabaiM Y Sherman
Nov 21, 1997·Biochemical and Biophysical Research Communications·T W SchulteL M Neckers
Jan 8, 1999·Cell Stress & Chaperones·A Samali, S Orrenius
Mar 30, 1999·Experimental Cell Research·M Jäättelä
Jun 9, 1999·Proceedings of the National Academy of Sciences of the United States of America·C JollyR I Morimoto
Sep 20, 2000·Proceedings of the National Academy of Sciences of the United States of America·S SatoT Tsuruo
Oct 6, 2000·Journal of the National Cancer Institute·C Jolly, R I Morimoto
Jan 10, 2002·The Journal of Biological Chemistry·Naoya FujitaTakashi Tsuruo

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Citations

Dec 17, 2014·International Journal of Oncology·Zuzana SolárováPeter Solár
Aug 25, 2010·Annals of Surgical Oncology·Yoshiaki KitaMasaki Mori

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