Acta Pharmacologica Sinica 2006 June; 27 (6): 694-699; doi: 10.1111/j.1745-7254.2006.00326.x

Aim: To investigate the effects of curcumin (Cur) on p210^bcr/abl level in K562 cells, and the relationship between these effects and the molecular chaperone functions of heat shock protein 90 (Hsp90).

Methods: Flow cytometry and Western blot were used to examine the abundance of p210^bcr/abl, Hsp90, p23, Hsp70, and p60^Hop in K562 cells treated with Cur. Reverse transcription polymerase chain reaction (RT-PCR) was used to determine the bcr-abl mRNA level in K562 cells treated with Cur. After co-immunoprecipitation of p210^bcr/abl and its molecular chaperones, the immunoprecipitate was then subjected to Western blot analysis with anti-Hsp90, anti-Hsp70, anti-p23, and anti-p60^HopmAb.

Results: An exposure of K562 cells to Cur produced time-dependent down-regulation of p210^bcr/abl, the inhibition rate of p210^bcr/abl in K562 cells determined by flow cytometry after treatment with Cur 27.2 µmol/L for 1 h, 6 h, 12 h and 24 h was 31.2%, 63.7%, 81.3% and 94.5%, respectively. In contrast, Cur had almost no influence on bcr-abl mRNA level. Treatment with Cur for 24 h reduced the association of p210^bcr/abl with Hsp90/p23 complex, while increasing the association of p210^bcr/abl with Hsp70/p60^Hop complex; however, the total protein abundance of Hsp90, p23, and p60^Hop in K562 cells had no apparent change, while Hsp70 increased greatly.

Conclusion: Down-regulation of p210^bcr/abl by Cur involves dissociating the binding of p210^bcr/abl with Hsp90/p23 complex. In contrast, the association of p210^bcr/abl with Hsp70/p60^Hop complex increased.

Keywords: curcumin; molecular chaperones; bcr-abl fusion proteins; heat shock protein 90