|
|
|
| Curcumin inhibits JAK2/STAT signaling through increasing the expression of SOCS in myeloproliferative neoplasms |
Department of Hematology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325015
|
|
| Cite this article: |
|
XING Chongyun,ZHOU Lin,ZHUANG Qiang, et al. Curcumin inhibits JAK2/STAT signaling through increasing the expression of SOCS in myeloproliferative neoplasms[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2015, 45(10 ): 718-.
|
|
|
Abstract Objective: To investigate the mechanism of curcumin in inhibiting JAK2/STAT signaling through increasing the expression of SOCS1/3 in myeloproliferative neoplasms. Methods: JAK2/STAT signaling and protein levels of SOCS1/3 were detected by Western blotting in HEL and 32D. Acetylation of histone in the regions of SOCS1/3 promoter was detected by immunoprecipitation assay. Furthermore, HDAC enzyme activity was detected by colorimetric HDAC activity assay kit. Results: Curcumin inhibited JAK2/STAT signaling in HEL and 32D cells in vitro. Curcumin could inhibite HDAC enzyme activities and decreased the levels of HDAC1, 3 and 8. Curcumin elevated the mRNA and protein levels of SOCS1/3 via triggering acetylation of histone in the regions of SOCS1/3 promoter. Conclusion: Taken together, our data uncover a regulatory mechanism of SOCS1/3 through inhibition of HDAC activity by curcumin.
|
|
Received: 12 March 2015
|
| |
|
|
|
[1] Greenhalgh CJ, Hilton DJ. Negative regulation of cytokine signaling[J]. J Leukoc Biol, 2001, 70(3): 348-356.
[2] James C, Ugo V, Le Couedic JP, et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycy thaemia vera[J]. Nature, 2005, 434(7037): 1144-1148.
[3] Pardanani AD, Levine RL, Lasho T, et al. MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients[J]. Blood, 2006, 108(10): 3472-3476.
[4] Hookham MB, Elliott J, Suessmuth Y, et al. The myeloproliferative disorder-associated JAK2 V617F mutant escapes negative regulation by suppressor of cytokine signaling 3[J]. Blood, 2007, 109(11): 4924-4929.
[5] Senese S, Zaragoza K, Minardi S, et al. Role for histone deacetylase 1 in human tumor cell proliferation[J]. Mol Cell Biol, 2007, 27(13): 4784-4795.
[6] Halkidou K, Gaughan L, Cook S, et al. Upregulation and nuclear recruitment of HDAC1 in hormone refractory pros tate cancer[J]. The Prostate, 2004, 59(2): 177-189.
[7] Marks PA. The clinical development of histone deacety- lase inhibitors as targeted anticancer drugs[J]. Expert Opin Investig Drugs, 2010, 19(9): 1049-1066.
[8] Prince HM, Bishton MJ, Harrison SJ. Clinical studies of histone deacetylase inhibitors[J]. Clin Cancer Res, 2009, 15(12): 3958-3969.
[9] Slingerland M, Guchelaar HJ, Gelderblom H. Histone deacetylase inhibitors: an overview of the clinical studies in solid tumors[J]. Anticancer Drugs, 2014, 25(2): 140-149.
[10] Kuttan R, Bhanumathy P, Nirmala K, et al. Potential anti- cancer activity of turmeric (Curcuma longa)[J]. Cancer Lett, 1985, 29(2): 197-202.
[11] 韩文文, 支绍册, 赵倩, 等. 姜黄素对急性百草枯中毒大鼠肝损伤中炎症反应的影响和机制[J]. 中国急救医学, 2015 (1): 62-67.
[12] 刘双, 程建华, 韩钊, 等. 姜黄素对局灶脑缺血再灌注损伤的神经保护作用及对新生神经细胞增殖的影响[J]. 温州医学院学报, 2013, 43(3): 171-174.
[13] Lee SJ, Krauthauser C, Maduskuie V, et al. Curcumin-indu ced HDAC inhibition and attenuation of medulloblastoma growth in vitro and in vivo[J]. BMC Cancer, 2011, 11: 144.
[14] Mackenzie GG, Queisser N, Wolfson ML, et al. Curcumin induces cell-arrest and apoptosis in association with the in hibition of constitutively active NF-kappaB and STAT3pathways in Hodgkin’s lymphoma cells[J]. Int J Cancer, 2008, 123(1): 56-65.
[15] Blasius R, Reuter S, Henry E, et al. Curcumin regulates sig nal transducer and activator of transcription (STAT) expression in K562 cells[J]. Biochem Pharmacol, 2006, 72(11): 1547-1554.
[16] Yang CL, Liu YY, Ma YG, et al. Curcumin blocks small cell lung cancer cells migration, invasion, angiogenesis,cell cycle and neoplasia through Janus Kinase-STAT3 sig-nalling pathway[J]. PLoS One, 2012, 7(5): e37960.
[17] Seo JH, Jeong KJ, Oh WJ, et al. Lysophosphatidic acid induces STAT3 phosphorylation and ovarian cancer cell motility: their inhibition by curcumin[J]. Cancer Lett, 2010, 288(1): 50-56.
[18] Rajasingh J, Raikwar HP, Muthian G, et al. Curcumin indu ces growth-arrest and apoptosis in association with the in- hibition of constitutively active JAK-STAT pathway in T
cell leukemia[J]. Biochem Biophys Res Commun, 2006, 340
(2): 359-368.
[19] Capello D, Deambrogi C, Rossi D, et al. Epigenetic inacti vation of suppressors of cytokine signalling in Philadelphianegative chronic myeloproliferative disorders[J]. Br J Hae matol, 2008, 141(4): 504-511.
[20] Fourouclas N, Li J, Gilby DC, et al. Methylation of the suppressor of cytokine signaling 3 gene (SOCS3) in myelopro- liferative disorders[J]. Haematologica, 2008, 93(11): 1635-1644.
[21] Xiong H, Du W, Zhang YJ, et al. Trichostatin A, a histone deacetylase inhibitor, suppresses JAK2/STAT3 signaling via inducing the promoter-associated histone acetylation of SOCS1 and SOCS3 in human colorectal cancer cells[J]. Mol Carcinog, 2012, 51(2): 174-184.
[22] Akada H, Akada S, Gajra A, et al. Efficacy of vorinostat in a murine model of polycythemia vera[J]. Blood, 2012, 119 (16): 3779-3789.
[23] Liu HY, Chen Y, Cui GH, et al. Curcumin, a potent anti-tumor reagent, is a novel histone deacetylase inhibitor regulating B-NHL cell line Raji proliferation[J]. Acta Pharmacol Sin, 2005, 26(3): 603-609.
[24] Yan G, Graham K, Lanza-Jacoby S. Curcumin enhances the anticancer effects of trichostatin a in breast cancer cells[J]. Mol Carcinog, 2013, 52(5): 404-411.
[25] Giommarelli C, Zuco V, Favini E, et al. The enhancement of antiproliferative and proapoptotic activity of HDAC inhibi tors by curcumin is mediated by Hsp90 inhibition[J]. Cell Mol Life Sci, 2010, 67(6): 995-1004.
|
|
|
|
