title: Tumor necrosis factor-alpha enhances DMSO-induced differentiation of HL-60 cells through the activation of ERK/MAPK pathway.
abstract: The differentiation of promyelocytic leukemic cells into mature cells is the major strategy for drug-based treatment of leukemia. Higher efficient methods to differentiate promyelocytic leukemic cells have been developed using various differentiation inducers including interferon-alpha, interleukin-4, tumor necrosis factor-alpha (TNF-alpha), and dimethyl sulfoxide (DMSO) as a single agent or in combination with each other. Here, we show that a combination of TNF-alpha with DMSO shows a synergic effect on HL-60 cell differentiation through the activation of ERK pathway. TNF-alpha enhanced CD11b expression and percent of cell population in the G1 phase induced by DMSO, which are hallmarks for HL-60 cell differentiation. Inhibition of ERK pathway abolished the synergic effect of TNF-alpha in combination with DMSO on HL-60 differentiation, but the inhibition NF-kappaB pathway did not. These results suggest that TNF-alpha synergistically increases DMSO-induced differentiation of HL-60 cells through the activation of ERK/MAPK-signaling pathway.
authors.affiliation: Department of Biochemistry, Institute of Medical Science, Chonbuk National University Medical School, Jeonju, Jeonbuk, 560-180, South Korea.
authors.forename: Hong-Nu
authors.initials: HN
authors.lastname: Yu
authors.affiliation: Department of Biochemistry, Institute of Medical Science, Chonbuk National University Medical School, Jeonju, Jeonbuk, 560-180, South Korea.
authors.forename: Young-Rae
authors.initials: YR
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, Institute of Medical Science, Chonbuk National University Medical School, Jeonju, Jeonbuk, 560-180, South Korea.
authors.forename: Eun-Mi
authors.initials: EM
authors.lastname: Noh
authors.affiliation: Department of Biochemistry, Institute of Medical Science, Chonbuk National University Medical School, Jeonju, Jeonbuk, 560-180, South Korea.
authors.forename: Kyung-Sun
authors.initials: KS
authors.lastname: Lee
authors.affiliation: Department of Microbiology and Immunology, Chonbuk National University Medical School, Jeonju, South Korea.
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Song
authors.affiliation: Department of Microbiology and Immunology, Chonbuk National University Medical School, Jeonju, South Korea.
authors.forename: Myung-Kwan
authors.initials: MK
authors.lastname: Han
authors.affiliation: Department of Internal Medicine, Research Center for Allergic Immune Diseases, Chonbuk National University Medical School, Jeonju, South Korea.
authors.forename: Yong-Chul
authors.initials: YC
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Research Center for Allergic Immune Diseases, Chonbuk National University Medical School, Jeonju, South Korea.
authors.forename: Chang-Yeol
authors.initials: CY
authors.lastname: Yim
authors.affiliation: Division of Hematology/Oncology, Gachon University Medical Center, Inchon, South Korea.
authors.forename: Jinny
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Companion and Laboratory Animal Science, Kongju National University, Kongju, South Korea.
authors.forename: Byeong-Soo
authors.initials: BS
authors.lastname: Kim
authors.affiliation: Department of Companion and Laboratory Animal Science, Kongju National University, Kongju, South Korea.
authors.forename: Sung-Ho
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Pharmacy, College of Pharmacy, Ewha Womans University, Seoul, South Korea.
authors.forename: Seung Jin
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, Institute of Medical Science, Chonbuk National University Medical School, Jeonju, Jeonbuk, 560-180, South Korea. jsukim@chonbuk.ac.kr.
authors.forename: Jong-Suk
authors.initials: JS
authors.lastname: Kim
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D042381:Granulocyte Precursor Cells / Q000187:drug effects*; D018922:HL-60 Cells; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D019950:Mitogen-Activated Protein Kinase 1 / Q000187:drug effects; D048052:Mitogen-Activated Protein Kinase 3 / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D004121:Dimethyl Sulfoxide