Tumor necrosis factor-alpha enhances DMSO-induced differentiation of HL-60 cells through the activation of ERK/MAPK pathway.
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.
Yu
Hong-Nu
HN
Department of Biochemistry, Institute of Medical Science, Chonbuk National University Medical School, Jeonju, Jeonbuk, 560-180, South Korea.
Lee
Young-Rae
YR
Department of Biochemistry, Institute of Medical Science, Chonbuk National University Medical School, Jeonju, Jeonbuk, 560-180, South Korea.
Noh
Eun-Mi
EM
Department of Biochemistry, Institute of Medical Science, Chonbuk National University Medical School, Jeonju, Jeonbuk, 560-180, South Korea.
Lee
Kyung-Sun
KS
Department of Biochemistry, Institute of Medical Science, Chonbuk National University Medical School, Jeonju, Jeonbuk, 560-180, South Korea.
Song
Eun-Kyung
EK
Department of Microbiology and Immunology, Chonbuk National University Medical School, Jeonju, South Korea.
Han
Myung-Kwan
MK
Department of Microbiology and Immunology, Chonbuk National University Medical School, Jeonju, South Korea.
Lee
Yong-Chul
YC
Department of Internal Medicine, Research Center for Allergic Immune Diseases, Chonbuk National University Medical School, Jeonju, South Korea.
Yim
Chang-Yeol
CY
Department of Internal Medicine, Research Center for Allergic Immune Diseases, Chonbuk National University Medical School, Jeonju, South Korea.
Park
Jinny
J
Division of Hematology/Oncology, Gachon University Medical Center, Inchon, South Korea.
Kim
Byeong-Soo
BS
Department of Companion and Laboratory Animal Science, Kongju National University, Kongju, South Korea.
Lee
Sung-Ho
SH
Department of Companion and Laboratory Animal Science, Kongju National University, Kongju, South Korea.
Lee
Seung Jin
SJ
Department of Pharmacy, College of Pharmacy, Ewha Womans University, Seoul, South Korea.
Kim
Jong-Suk
JS
Department of Biochemistry, Institute of Medical Science, Chonbuk National University Medical School, Jeonju, Jeonbuk, 560-180, South Korea. jsukim@chonbuk.ac.kr.
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*
D014409:Tumor Necrosis Factor-alpha; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D004121:Dimethyl Sulfoxide