Abstract
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 p210bcr/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/Lfor 1 h, 6 h, 12 hand 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 inK562 cells had no apparent change, while Hsp70 increased greatly.
Conclusion:
Down-regulation of p210bcr/abl 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.
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References
Chiosis G, Vilenchik M, Kim J, Solit D . Hsp90: the vulnerable chaperone. Drug Discov Today 2004; 9: 881–8.
Sharma SV, Agatsuma T, Nakano H . Targeting of the protein chaperone, HSP90, by the transformation suppressing agent, radicicol. Oncogene 1998; 16: 2639–45.
Marcu MG, Schulte TW, Neckers L . Novobiocin and related coumarins and depletion of heat shock protein 90-dependent signaling proteins. J Natl Cancer Inst 2000; 92: 242–8.
Shiotsu Y, Neckers LM, Wortman I, An WG, Schulte TW, Soga S, et al. Novel oxime derivatives of radicicol induce erythroid differentiation associated with preferential G(1) phase accumulation against chronic myelogenous leukemia cells through de-stabilization of Bcr-Abl with Hsp90 complex. Blood 2000; 96: 2284–91.
An WG, Schulte TW, Neckers LM . The heat shock protein 90 antagonist geldanamycin alters chaperone association with p21 0bcr/abl and v-src proteins before their degradation by the proteasome. Cell Growth Differ 2000; 11: 355–60.
Pane F, Intrieri M, Quintarellil C, Izzo B, Muccioli GC, Salvatore F . BCR/ABL genes and leukemic phenotype: from molecular mechanisms to clinical correlations. Oncogene 2002; 21: 8652–67.
Squires MS, Hudson EA, Howells L, Sale S, Houghton CE, Jones JL, et al. Relevance of mitogen activated protein kinase (MAPK) and phosphotidylinositol-3-kinase/protein kinase B (PI3K/PKB) pathways to induction of apoptosis by curcumin in breast cells. Biochem Pharmacol 2003; 65: 361–76.
Ammon HPT, Wahl MA . Pharmacology of Curcuma longa. Planta Med 1991; 57: 1–7.
Liao S, Lin J, Dang MT, Zhang H, Kao YH, Fukuchi J, et al. Growth suppression of hamster flank organs by topical application of catechins, alizarin, curcumin, and myristoleic acid. Arch Dermatol Res 2001; 293: 200–5.
Wu LX, Xu JH, Wu GH, Chen YZ . Inhibitory effect of curcumin on proliferation of K562 cells involves down-regulation of p210 (bcr/abl) initiated Ras signal transduction pathway. Acta Pharmacol Sin 2003; 24: 1155–60.
Melo JV, Gordon DE, Cross NC, Goldman JM . The ABL-BCR fusion gene is expressed in chronic myeloid leukemia. Blood 1993; 81: 158–65.
Korutla L, Kumar R . Inhibitory effect of curcumin on epidermal growth factor receptor kinase activity in A431 cells. Biochim Biophys Acta 1994; 1224: 597–600.
Lin JK, Pan MH, Lin-Shiau SY . Recent studies on the biofunctions and biotransformations of curcumin. Biofactors 2000; 13: 153–8.
Hong RL, Spohn WH, Hung MC . Curcumin inhibits tyrosine kinase activity of p1 85neu and also depletes p1 85neu. Clin Cancer Res 1999; 5: 1884–91.
Spiller DG, Giles RV, Broughton CM, Grzybowski J, Ruddell CJ, Tidd DM, et al. The influence of target protein half-life on the effectiveness of antisense oligonucleotide analog-mediated biologic responses. Antisense Nucleic Acid Drug Dev 1998; 8: 281–93.
Blagosklonny MV, Toretsky J, Neckers LM . Geldanamycin selectively destabilizes and conformationally alters mutated p53. Oncogene 1995; 11: 933–9.
Schneider C, Sepp-Lorenzino L, Nimmesgern E, Ouerfelli O, Danishefsky S, Rosen N, et al. Pharmacologic shifting of a balance between protein refolding and degradation mediated by Hsp90. Proc Natl Acad Sci USA 1996; 93: 14536–41.
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Project supported by the National Natural Science Foundation of China (No 30171158 and No 30472187) and the Natural Science Foundation of Fujian Province, China (No C992001).
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Wu, Lx., Xu, Jh., Huang, Xw. et al. Down-regulation of p210bcr/abl by curcumin involves disrupting molecular chaperone functions of Hsp90. Acta Pharmacol Sin 27, 694–699 (2006). https://doi.org/10.1111/j.1745-7254.2006.00326.x
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DOI: https://doi.org/10.1111/j.1745-7254.2006.00326.x
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