Curcumin's Biphasic Hormetic Response on Proteasome Activity and Heat-Shock Protein Synthesis in Human Keratinocytes

Curcumin (diferuloylmethane), is a component of the yellow powder prepared from the roots of Curcuma longa (Zingiberaceae), also known as tumeric or turmeric. It is widely cultivated and used as a food ingredient in tropical areas of Asia and Central America. Treatment of mid-passage human epidermal keratinocytes with curcumin resulted in a biphasic hormetic dose-response with respect to proteasome activity. Curcumin treatment (up to 1 mu M for 24 h) increased chymotrypsin-like activity by 46% compared to that in untreated keratinocytes. However, higher concentrations of curcumin were inhibitory, and at 10 mu M the proteasome activity decreased to 46% of its initial value. Furthermore, the preincubation of human keratinocytes at 43 degrees C for 1 h, followed by 24-h treatment with 3 mu M curcumin, led to an increase in heat-shock protein (hsp70 and hsp90) levels by 24% and 19%, respectively, and the effect was sustained at concentrations up to 10 mu M. On the other hand, the level of the small hsp27 was unaffected by curcumin concentrations of 0.3-1 mu M, while it decreased by 34% at 10 mu M.