Curcumin regulates signal transducer and activator of transcription (STAT) expression in K562 cells

• Published in: Biochemical pharmacology Vol. 72; no. 11; pp. 1547 - 1554
• Main Authors: Blasius, Romain, Reuter, Simone, Henry, Estelle, Dicato, Mario, Diederich, Marc
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 30.11.2006; Elsevier Science
• Subjects: Antineoplastic Agents - pharmacology; Biological and medical sciences; Cell Nucleus - drug effects; Cell Nucleus - metabolism; Curcumin; Curcumin - pharmacology; Drug Combinations; Gene Expression Regulation, Neoplastic - drug effects; Hematologic and hematopoietic diseases; Humans; IFN; Interferon-beta - pharmacology; Interferon-gamma; K562; K562 Cells; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - metabolism; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; Pharmacology. Drug treatments; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; Signal Transduction - drug effects; STAT; STAT Transcription Factors - genetics; STAT Transcription Factors - metabolism; Transcriptional Activation - drug effects; IFN; STAT; IL; K562; Jak; FCS; Curcumin; ISRE; Human; Transcription; Leukemia; Cytokine; Malignant hemopathy; Signal transduction; Cell line; Activator; Established cell line; Interferon; Transduction factor STAT; Tumor cell
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/j.bcp.2006.07.029

Signal transducers and activators of transcription (STATs) play important roles in numerous cellular events as for example differentiation, inflammation or immune response. Furthermore, constitutive STAT activation can be observed in a high number of tumors. In our hands, curcumin treatment induced a decrease of nuclear STAT3, -5a and -5b, without affecting neither STAT1, nor the phosphorylation state of STAT1, -3 or -5 in the K562 cell line. Most interestingly, the decrease of nuclear STAT5a and -5b after curcumin treatment was accompanied by an increase of truncated STAT5 isoforms, indicating that curcumin is able to induce the cleavage of STAT5 into its dominant negative variants lacking the STAT5 C-terminal region. Interferon (IFN)-β and -γ treatment induced IFN-stimulated responsive element (ISRE) transcriptional activity, which was efficiently inhibited by curcumin pre-treatment. In parallel, IFN-γ treatment induced an increase of the amount of nuclear STAT1 and -3, as well as their phosphorylated isoforms. Again, curcumin pre-treatment inhibited these increases. Finally, curcumin treatment inhibited Jak2 mRNA expression as well as cyclin D1 and v-src gene expression in K562 chronic leukaemia cells.