title: Curcumin induces cell-arrest and apoptosis in association with the inhibition of constitutively active NF-kappaB and STAT3 pathways in Hodgkin's lymphoma cells.
abstract: Although treatment of Hodgkin's lymphoma (HL) with a multi-drug approach has been very successful, its toxicity becomes evident after several years as secondary malignancies and cardiovascular disease. Therefore, the current goal in HL treatment is to find new therapies that specifically target the deregulated signaling cascades, such as NF-kappaB and STAT3, which cause Hodgkin and Reed-Sternberg (H-RS) cell proliferation and resistance of apoptosis. Based on the above information, we investigated the capacity of curcumin to inhibit NF-kappaB and STAT3 in H-RS cells, characterizing the functional consequences. Curcumin is incorporated into H-RS cells and acts inhibiting both NF-kappaB and STAT3 activation, leading to a decreased expression of proteins involved in cell proliferation and apoptosis, e.g. Bcl-2, Bcl-xL, cFLIP, XIAP, c-IAP1, survivin, c-myc and cyclin D1. Interestingly, curcumin caused cell cycle arrest in G2-M and a significant reduction (80-97%) in H-RS cell viability. Furthermore, curcumin triggered cell death by apoptosis, as evidenced by the activation of caspase-3 and caspase-9, changes in nuclear morphology and phosphatidylserine translocation. The above findings provide a mechanistic rationale for the potential use of curcumin as a therapeutic agent for patients with HL.
authors.affiliation: Department of Nutrition, University of California, Davis, CA 95616, USA.
authors.forename: Gerardo G
authors.initials: GG
authors.lastname: Mackenzie
authors.forename: Nina
authors.initials: N
authors.lastname: Queisser
authors.forename: Manuel L
authors.initials: ML
authors.lastname: Wolfson
authors.forename: Cesar G
authors.initials: CG
authors.lastname: Fraga
authors.forename: Ana M
authors.initials: AM
authors.lastname: Adamo
authors.forename: Patricia I
authors.initials: PI
authors.lastname: Oteiza
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003474:Curcumin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D024202:Electrophoretic Mobility Shift Assay; D004789:Enzyme Activation; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D010718:Phosphatidylserines / Q000235:genetics; D016539:Reed-Sternberg Cells / Q000187:drug effects / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014178:Translocation, Genetic
chemical_list: D000970:Antineoplastic Agents; D016328:NF-kappa B; D010718:Phosphatidylserines; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D053148:Caspase 3; D053453:Caspase 9; D003474:Curcumin