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Aryl Hydrocarbon Receptor Antagonist StemRegenin 1 Promotes the Expansion of Human Promyelocytic Leukemia Cell Line,
Ryohei Koide1, Kasem Kulkeaw1, Yuka Tanaka2
1Department of Research and Development of Next Generation Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan.
Background/Aim:
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.
Materials And 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.
Conclusion:
SR1 promotes the expansion of NB4 cells in vitro, implying the need for caution regarding in vivo use of R1.
