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

Author： Akimoto T.   Nonaka T.   Harashima K.   Sakurai H.   Ishikawa H.   Mitsuhashi N.  

Publisher： Informa Healthcare

ISSN： 1362-3095

Source： International Journal of Radiation Biology, Vol.80, Iss.7, 2004-07, pp. : 483-492

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Abstract

Purpose: 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.Materials and methods: 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.Results: 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.Conclusions: 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 that the Hsp90 chaperone complex could be a new molecular target for the modification of the cellular response to heat.

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