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
  • View Affiliations

  • 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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January 2018
Volume 39 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

2016 Impact Factor: 2.662
Ranked #31/217 Oncology
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APA
Yang, J., Lee, C., Cho, H., Lu, C., Kuo, S., Wen, Y. ... Tsai, S. (2018). ITR‑284 modulates cell differentiation in human chronic myelogenous leukemia K562 cells. Oncology Reports, 39, 383-391. https://doi.org/10.3892/or.2017.6090
MLA
Yang, J., Lee, C., Cho, H., Lu, C., Kuo, S., Wen, Y., Tsai, F., Lee, M., Tsai, S."ITR‑284 modulates cell differentiation in human chronic myelogenous leukemia K562 cells". Oncology Reports 39.1 (2018): 383-391.
Chicago
Yang, J., Lee, C., Cho, H., Lu, C., Kuo, S., Wen, Y., Tsai, F., Lee, M., Tsai, S."ITR‑284 modulates cell differentiation in human chronic myelogenous leukemia K562 cells". Oncology Reports 39, no. 1 (2018): 383-391. https://doi.org/10.3892/or.2017.6090