Curcumin suppresses growth and induces apoptosis in primary effusion lymphoma

• Published in: Oncogene Vol. 24; no. 47; pp. 7022 - 7030
• Main Authors: UDDIN, Shahab, HUSSAIN, Azhar R, MANOGARAN, Pulicat S, AL-HUSSEIN, Khaled, PLATANIAS, Leonidas C, GUTIERREZ, Marina I, BHATIA, Kishor G
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 27.10.2005; Nature Publishing Group
• Subjects: Ageing, cell death; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Biological and medical sciences; Cancer; Caspase 3; Caspases - metabolism; Cell activation; Cell cycle; Cell death; Cell physiology; Cell proliferation; Cell Proliferation - drug effects; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Curcuma; Curcumin; Curcumin - pharmacology; Cytochrome c; Cytochromes c - metabolism; DNA-Binding Proteins - metabolism; Effusion; Enzyme Activation - drug effects; Fundamental and applied biological sciences. Psychology; Hematologic and hematopoietic diseases; Humans; Janus kinase; Janus Kinase 1; Kinases; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoma; Lymphoma - drug therapy; Lymphoma - metabolism; Lymphoma - pathology; Medical sciences; Membrane potential; Membrane Potentials - drug effects; Mitochondria; Mitochondria - drug effects; Molecular and cellular biology; Pleural Effusion, Malignant - drug therapy; Pleural Effusion, Malignant - metabolism; Pleural Effusion, Malignant - pathology; Poly(ADP-ribose) polymerase; Poly(ADP-ribose) Polymerases - metabolism; Primary effusion lymphoma; Protein-Tyrosine Kinases - metabolism; Ribose; Signal Transduction - drug effects; Stat3 protein; STAT3 Transcription Factor; Trans-Activators - metabolism; Tumor Cells, Cultured; Saudi Arabia; United States > US; Riyadh Saudi Arabia; Growth; Cell death; Lymphoproliferative syndrome; PEL; NHL therapy; Malignant hemopathy; Non Hodgkin lymphoma; Primary effusion lymphoma; Carcinogenesis; Apoptosis; curcumin
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1208864

The mechanisms that regulate induction of the antiapoptotic state and mitogenic signals in primary effusion lymphoma (PEL) are not well known. In efforts to identify novel approaches to block the proliferation of PEL cells, we found that curcumin (diferuloylmethane), a natural compound isolated from the plant Curcuma Ionga, inhibits cell proliferation and induces apoptosis in a dose dependent manner in several PEL cell lines. Such effects of curcumin appear to result from suppression of the constitutively active STAT3 through inhibition of Janus kinase 1 (JAK1). Our data also demonstrate that curcumin induces loss of mitochondrial membrane potential with subsequent release of cytochrome c and activation of caspase-3, followed by polyadenosin-5'-diphosphate-ribose polymerase (PARP) cleavage. Altogether, our findings suggest a novel function for curcumin, acting as a suppressor of JAK-1 and STAT3 activation in PEL cells, leading to inhibition of proliferation and induction of caspase-dependent apoptosis. Therefore, curcumin may have a future therapeutic role in PEL and possibly other malignancies with constitutive activation of STAT3.