title: Aryl Hydrocarbon Receptor Antagonist StemRegenin 1 Promotes the Expansion of Human Promyelocytic Leukemia Cell Line, NB4.
abstract: OBJECTIVE
  StemRegenin 1 (SR1), an antagonist of aryl hydrocarbon receptor (AHR), reportedly promotes expansion of hematopoietic stem cells but its effect on leukemia cells is unclear. This study focused on the role of SR1 in leukemia cell proliferation.
  
  
  METHODS
  AHR expression was compared in the cell lines Jurkat, Kasumi-1, NB4 and K562, using real-time polymerase chain reaction. Highly AHR-expressing NB4 cells were cultured with SR1 for 2 and 4 days, and evaluated for viability and gene expression. DNA microarray was also performed.
  
  
  RESULTS
  The viability of NB4 cells treated with 1.5 μM SR1 increased at day 4. Expression of B-cell CLL/lymphoma 2 (BCL2) was up-regulated, while that of BCL2 associated X protein (BAX) was down-regulated at day 2. Increased cyclin D1 (CCND1), CCND2 and v-myc avian myelocytomatosis viral oncogene homolog (MYC) expressions were observed at day 4. Global gene expression profiles showed up-regulation of splice variant-related genes and down-regulation of inflammation-related genes.
  
  
  CONCLUSIONS
  SR1 promotes the expansion of NB4 cells in vitro, implying the need for caution regarding in vivo use of R1.
authors.affiliation: Department of Research and Development of Next Generation Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Ryohei
authors.initials: R
authors.lastname: Koide
authors.affiliation: Department of Research and Development of Next Generation Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Kasem
authors.initials: K
authors.lastname: Kulkeaw
authors.affiliation: Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Department of Research and Development of Next Generation Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan Center for Clinical and Translational Research, Kyushu University, Fukuoka, Japan.
authors.forename: Anthony
authors.initials: A
authors.lastname: Swain
authors.affiliation: Center for Clinical and Translational Research, Kyushu University, Fukuoka, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakanishi
authors.affiliation: Department of Research and Development of Next Generation Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan Center for Clinical and Translational Research, Kyushu University, Fukuoka, Japan Center for Advanced Medical Innovation, Kyushu University, Fukuoka, Japan ds-mons@yb3.so-net.ne.jp.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sugiyama
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute; D011687:Purines / Q000494:pharmacology*; D018336:Receptors, Aryl Hydrocarbon / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D011687:Purines; D018336:Receptors, Aryl Hydrocarbon; C552240:StemRegenin 1
keywords: Aryl hydrocarbon receptor; NB4 cells; StemRegenin 1