title: Pure curcumin increases the expression of SOCS1 and SOCS3 in myeloproliferative neoplasms through suppressing class I histone deacetylases.
abstract: Suppressors of cytokine signaling, SOCS1 and SOCS3, are important negative regulators of Janus kinase 2/signal transducers and activators of transcription signaling, which is constitutively activated in myeloproliferative neoplasms (MPNs) and leukemia. Curcumin has been shown to possess anticancer activity through different mechanisms. However, whether curcumin can regulate the expression of SOCS1 and SOCS3 is still unknown. Here, we found that curcumin elevated the expression of SOCS1 and SOCS3 via triggering acetylation of histone in the regions of SOCS1 and SOCS3 promoter in K562 and HEL cells. As a novel histone deacetylases (HDACs) inhibitor, curcumin inhibited HDAC enzyme activities and decreased the levels of HDAC1, 3 and 8 but not HDAC2. Knockdown of HDAC8 by small interfering RNA markedly elevated the expression of SOCS1 and SOCS3. Moreover, ectopic expression of HDAC8 decreased the levels of SOCS1 and SOCS3. Thus, HDAC8 plays an important role in the modulation of SOCS1 and SOCS3 by curcumin. Also, trichostatin A (TSA), an inhibitor of HDACs, increased the levels of SOCS1 and SOCS3. Furthermore, curcumin increased the transcript levels of SOCS1 and SOCS3 and significantly inhibited the clonogenic activity of hematopoietic progenitors from patients with MPNs. Finally, curcumin markedly inhibited HDAC activities and decreased HDAC8 levels in primary MPN cells. Taken together, our data uncover a regulatory mechanism of SOCS1 and SOCS3 through inhibition of HDAC activity (especially HDAC8) by curcumin. Thus, being a relative non-toxic agent, curcumin may offer a therapeutic advantage in the clinical treatment for MPNs.
authors: Laboratory of Internal Medicine and 2Department of Hematology, The First Affiliated Hospital of Wenzhou Medical College, 2 FuXue Road, Wenzhou 325000, China.
authors: Chi-qi
authors: CQ
authors: Chen
authors: Kang
authors: K
authors: Yu
authors: Qing-xian
authors: QX
authors: Yan
authors: Chong-yun
authors: CY
authors: Xing
authors: Yi
authors: Y
authors: Chen
authors: Zhuang
authors: Z
authors: Yan
authors: Yi-fen
authors: YF
authors: Shi
authors: Ke-wen
authors: KW
authors: Zhao
authors: Shen-meng
authors: SM
authors: Gao
mesh_terms: D000107:Acetylation; D019046:Bone Marrow Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D003474:Curcumin / Q000494:pharmacology*; D004789:Enzyme Activation; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D053614:Janus Kinase 2 / Q000235:genetics / Q000378:metabolism; D020014:K562 Cells; D009196:Myeloproliferative Disorders / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D061251:Primary Cell Culture; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D034741:RNA, Small Interfering; D012097:Repressor Proteins; C108944:SOCS1 protein, human; C106644:SOCS3 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; C012589:trichostatin A; C507924:JAK2 protein, human; D053614:Janus Kinase 2; C409470:HDAC8 protein, human; D006655:Histone Deacetylases; D003474:Curcumin