title: Cyclodextrin-complexed curcumin exhibits anti-inflammatory and antiproliferative activities superior to those of curcumin through higher cellular uptake.
abstract: Curcumin, a yellow pigment present in the spice turmeric (Curcuma longa), has been linked with multiple beneficial activities, but its optimum potential is limited by poor bioavailability, in part due to the lack of solubility in aqueous solvents. To overcome the solubility problem, we have recently developed a novel cyclodextrin complex of curcumin (CDC) and examined here this compound for anti-inflammatory and antiproliferative effects. Using the electrophoretic mobility shift assay, we found that CDC was more active than free curcumin in inhibiting TNF-induced activation of the inflammatory transcription factor NF-kappaB and in suppressing gene products regulated by NF-kappaB, including those involved in cell proliferation (cyclin D1), invasion (MMP-9), and angiogenesis (VEGF). CDC was also more active than free curcumin in inducing the death receptors DR4 and DR5. Annexin V staining, cleavage of caspase-3 and PARP, and DNA fragmentation showed that CDC was more potent than free curcumin in inducing apoptosis of leukemic cells. Antiproliferative assays also demonstrated that CDC was more active than free curcumin in suppressing proliferation of various cancer cell lines. The cyclodextrin vehicle had no effect in these assays. Compared with free curcumin, CDC had a greater cellular uptake and longer half-life in the cells. Overall we demonstrated that CDC had superior attributes compared with free curcumin for cellular uptake and for antiproliferative and anti-inflammatory activities.
authors.affiliation: Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 143, Houston, TX 77030, USA.
authors.forename: Vivek R
authors.initials: VR
authors.lastname: Yadav
authors.forename: Sahdeo
authors.initials: S
authors.lastname: Prasad
authors.forename: Ramaswamy
authors.initials: R
authors.lastname: Kannappan
authors.forename: Jayaraj
authors.initials: J
authors.lastname: Ravindran
authors.forename: Madan M
authors.initials: MM
authors.lastname: Chaturvedi
authors.forename: Lauri
authors.initials: L
authors.lastname: Vaahtera
authors.forename: Jaakko
authors.initials: J
authors.lastname: Parkkinen
authors.forename: Bharat B
authors.initials: BB
authors.lastname: Aggarwal
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3; D049109:Cell Proliferation / Q000187:drug effects; D002477:Cells / Q000378:metabolism; D030024:Curcuma / Q000378:metabolism; D003474:Curcumin / Q000494:pharmacology*; D019938:Cyclin D1 / Q000494:pharmacology; D006207:Half-Life; D006801:Humans; D016328:NF-kappa B / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts
chemical_list: D000893:Anti-Inflammatory Agents; D016328:NF-kappa B; D010936:Plant Extracts; D019938:Cyclin D1; C012596:turmeric extract; D053148:Caspase 3; D003474:Curcumin