ITR‑284 modulates cell differentiation in human chronic myelogenous leukemia K562 cells

Yang,Jai-Sing; Lee,Chao-Ying; Cho,Hsin-Chung; Lu,Chi-Cheng; Kuo,Sheng-Chu; Wen,Yen-Fang; Tsai,Fuu-Jen; Lee,Miau-Rong; Tsai,Shih-Chang

doi:10.3892/or.2017.6090

ITR‑284 modulates cell differentiation in human chronic myelogenous leukemia K562 cells

Authors:
- Jai-Sing Yang
- Chao-Ying Lee
- Hsin-Chung Cho
- Chi-Cheng Lu
- Sheng-Chu Kuo
- Yen-Fang Wen
- Fuu-Jen Tsai
- Miau-Rong Lee
- Shih-Chang Tsai
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Affiliations: Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan, R.O.C., School of Pharmacy, China Medical University, Taichung, Taiwan, R.O.C., Department of Biological Science and Technology, China Medical University, Taichung, Taiwan, R.O.C., Chinese Medicinal Research and Development Center, China Medical University Hospital, China Medical University, Taichung, Taiwan, R.O.C., Medicinal Chemistry Laboratory, Biomedical Engineering Research Laboratories, Industrial Technology Research Institute, Hsinchu, Taiwan, R.O.C., Genetics Center, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, R.O.C., Department of Biochemistry, China Medical University, Taichung, Taiwan, R.O.C.
Published online on: November 9, 2017 https://doi.org/10.3892/or.2017.6090
Pages: 383-391

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Abstract

ITR‑284 is a carboxamide analog that can inhibit proliferation in human promyelocytic leukemia HL-60 cells. To understand the effects and molecular mechanisms of ITR‑284 in human erythromyeloblastoid leukemia, we treated K562 cells with different concentrations of ITR‑284 (0, 2, 4, 6, 8 and 10 nM) and all-trans retinoic acid (ATRA) (0, 0.1, 0.5, 1, 5 and 10 µM) for 24 h. The IC50 of ITR‑284 was ~10 nM in K562 cells treated for 24 h as determined by MTT assay. May-Grünwald-Giemsa staining and nitro blue tetrazolium (NBT) assays were used to determine cell morphology changes and differentiation after ITR‑284 and ATRA treatment. In addition, mRNA expression levels of hematopoietic factors, including GATA‑1, NF-E2 and GATA‑2, were elevated, while expression levels of BCR‑ABL were downregulated in K562 cells after 24 h of treatment with ITR‑284 as determined by quantitative reverse transcription polymerase chain reaction. In addition, western blot analyses showed that FOXM1, GLI 1 and c-MYC protein levels were decreased by ITR‑284. Taken together, our data show that ITR‑284 induced K562 cell differentiation, which led to decreased tumorigenesis. Our findings suggest that ITR‑284 could be a potential candidate for treating chronic myelogenous leukemia.

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