title: Curcumin nanodisk-induced apoptosis in mantle cell lymphoma.
abstract: Mantle cell lymphoma (MCL) is a pre-germinal center neoplasm characterized by cyclin D1 overexpression resulting from t(11;14)(q13;q32). Since MCL is incurable with standard lymphoma therapies, new treatment approaches are needed that target specific biologic pathways. In the present study, we investigated a novel drug delivery nanovehicle enriched with the bioactive polyphenol, curcumin (curcumin nanodisks; curcumin-ND). Cells treated with curcumin-ND showed a dose-dependent increase in apoptosis. This was accompanied by enhanced generation of reactive oxygen species (ROS). The antioxidant, N-acetylcysteine, inhibited curcumin-ND induced apoptosis, suggesting that ROS generation plays a role in curcumin action on MCL cells. Curcumin-ND decreased cyclin D1, pAkt, pIκBα, and Bcl(2) protein. In addition, enhanced FoxO3a and p27 expression as well as caspase-9, -3, and poly(ADP-ribose) polymerase (PARP) cleavage were observed. Curcumin-ND treatment led to enhanced G(1) arrest in two cultured cell models of MCL.
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. a-singh@northwestern.edu
authors.forename: Amareshwar T K
authors.initials: AT
authors.lastname: Singh
authors.forename: Mistuni
authors.initials: M
authors.lastname: Ghosh
authors.forename: Trudy M
authors.initials: TM
authors.lastname: Forte
authors.forename: Robert O
authors.initials: RO
authors.lastname: Ryan
authors.forename: Leo I
authors.initials: LI
authors.lastname: Gordon
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D003474:Curcumin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D019938:Cyclin D1 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D020522:Lymphoma, Mantle-Cell / Q000378:metabolism / Q000473:pathology; D049329:Nanostructures / Q000008:administration & dosage / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D019938:Cyclin D1; D011065:Poly(ADP-ribose) Polymerases; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3; D053453:Caspase 9; D003474:Curcumin; D000111:Acetylcysteine