Down-regulation of p210bcr/abl by curcumin involves disrupting molecular chaperone functions of Hsp90

• 来源期刊: 中国药理学报（英文版）
• 关键词: curcumin molecular chaperones bcr-abl fusion proteins heat shock protein 90
• 年，卷（期）: 2006,（6）
• 页码范围: 694-699
• 页数: 6页
• 语种: 英文

摘要

Aim: To investigate the effects of curcumin (Cur) on p210bcr/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 p210bcr/abl, Hsp90, p23, Hsp70, and p60Hop 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 p210tar/abl and its molecular chaperones, the immunoprecipitate was then subjected to Western blot analysis with anti-Hsp90, anti-Hsp70, anti-p23, and anti-p60HopmAb. Results: An exposure of K562 cells to Cur produced time-dependent down-regulation of p210bcr/abl, the inhibition rate of p210bcr/abl in K562 cells determined by flow cytometry after treatment with Cur 27.2 umol/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 p210bcr/abl with Hsp90/p23 complex, while increasing the association of p210bcr/abl with Hsp70/p60Hop complex; however, the total protein abundance of Hsp90, p23, and p60Hop in K562 cells had no apparent change, while Hsp70 increased greatly. Conclusion: Down-regulation of p210bcr/abi by Cur involves dissociating the binding of p210bcr/abl with Hsp90/p23 complex. In contrast, the association of p210bcr/abl with Hsp70/p60Hop complex increased.