Flavonoid Dihydroquercetin, unlike Quercetin, Fails to Inhibit Expression of Heat Shock Proteins under Conditions of Cellular Stress

K. R. Budagova¹, S. V. Zhmaeva², A. N. Grigor'ev², A. Ya. Goncharova², and A. E. Kabakov^1,2*

¹Medical Radiological Research Center, Russian Academy of Medical Sciences, ul. Koroleva 4, Obninsk 249036, Russia; fax: (095) 956-1440; E-mail: mrrc@obninsk.ru

²MEDBIOPHARM, Ltd, Inc., ul. Kurchatova 23a, Obninsk 249036, Russia; fax: (08439) 6-8192; E-mail: medbiopharm@medbiopharm.ru

^* To whom correspondence should be addressed.

Received January 23, 2003; Revision received March 10, 2003

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Modification by natural flavonoids quercetin and dihydroquercetin of the in vitro cell response to hyperthermal and chemical stress was studied. Quercetin completely inhibited the synthesis and intracellular accumulation of 70-kD heat shock protein (HSP70) in response to hyperthermia or to treatment with sodium arsenite, whereas dihydroquercetin in the same or higher doses had no such effect. Stress exposures under conditions of the quercetin-inhibited HSP70 expression significantly increased the percentage of dead and damaged cells compared to the same exposures in the absence of quercetin. On the contrary, dihydroquercetin virtually failed to increase the damage and death of the stress-exposed cells which displayed typical induction of HSP70. The findings suggest a new strategy for pharmacological use of these flavonoids with similar structure.

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KEY WORDS: bioflavonoids, taxifolin, chaperones, hyperthermia, adaptive response, tolerance

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