title: Reduction in Cell Viability and in Homeobox Protein Levels Following in Vitro Exposure to δ-tocopherol in Acute Myeloid Leukemia.
abstract: δ-Tocopherol (δ-T), the least prevalent tocopherol in our diet, was described to have a more potent anticancer activity in solid tumors compared to the other tocopherols. δ-T induces tumor cell death through peroxisome proliferator-activated receptor γ (PPAR-γ) induction, cyclin-D1 inhibition, and modulation of redox balance. Nevertheless, the role of δ-T in preventing or treating hematologic malignancies has not been studied. In this study, we screened the efficacy of δ-T against six cell lines representing a wide spectrum of hematologic malignancies: Jurkat (acute T-cell leukemia), K-562 (chronic myeloid leukemia), KG-1 [acute myeloid leukemia (AML)], THP-1 (acute monocytic leukemia), TOM-1 (acute lymphoblastic leukemia), and UMCL01-101 (AIDS-associated diffuse large B-cell lymphoma). Interestingly, the AML cell line KG-1 was the only one to be significantly affected at concentrations of δ-T as low as 20 µM. The antileukemic activity of δ-T in AML was verified in a set of primary cells collected from patients newly diagnosed with AML. Apoptotic induction and cell cycle arrest explained the efficacy of δ-T against KG-1 cells. The mechanism of cell growth inhibition of δ-T was through downregulation of cyclin-D1 and a set of homeobox proteins (HOXA9, PBX1, and Cdx2) that have a well-documented role in the pathobiology of AML.
authors.affiliation: a Department of Medicine , Tulane University , New Orleans , Louisiana , USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Collins
authors.affiliation: b Section of Hematology and Medical Oncology , Department of Medicine, Tulane University , New Orleans , Louisiana , USA.
authors.forename: Hana
authors.initials: H
authors.lastname: Safah
authors.affiliation: b Section of Hematology and Medical Oncology , Department of Medicine, Tulane University , New Orleans , Louisiana , USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Lobelle-Rich
authors.affiliation: c Department of Biomedical Sciences , Quillen College of Medicine, East Tennessee State University , Johnson City , Tennessee , USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Whaley
authors.affiliation: c Department of Biomedical Sciences , Quillen College of Medicine, East Tennessee State University , Johnson City , Tennessee , USA.
authors.forename: Sharon
authors.initials: S
authors.lastname: Campbell
authors.affiliation: b Section of Hematology and Medical Oncology , Department of Medicine, Tulane University , New Orleans , Louisiana , USA.
authors.forename: Nakhle S
authors.initials: NS
authors.lastname: Saba
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019938:Cyclin D1 / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells / Q000187:drug effects / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000378:metabolism*; D024505:Tocopherols / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; C530104:CCND1 protein, human; D018398:Homeodomain Proteins; D019938:Cyclin D1; C479072:delta-tocopherol; D024505:Tocopherols