Butein inhibits NF-κB, AP-1 and Akt activation in adult T-cell leukemia/lymphoma

  • Authors:
    • Chie Ishikawa
    • Masachika Senba
    • Naoki Mori
  • View Affiliations

  • Published online on: June 2, 2017     https://doi.org/10.3892/ijo.2017.4026
  • Pages: 633-643
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Abstract

Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia/lymphoma (ATLL) but there is no effective treatment for HTLV-1-associated diseases. Herein, we determined the effect of butein, a bioactive plant polyphenol, on cell growth, apoptosis and signaling pathways in HTLV-1-infected T-cell lines and on tumor growth in SCID mice. Treatment with butein caused a decrease in viability of HTLV-1-infected T-cell lines. T cells cultured with butein showed obvious apoptosis morphology, and cleavage of poly(ADP-ribose) polymerase with activation of caspase-3, -8 and -9. Pretreatment of cells with caspase inhibitor partially blocked butein-induced inhibition of cell viability. Butein also resulted in cell cycle arrest at G1 phase. Butein markedly downregulated the protein expression levels of CDK4, CDK6, cyclin D1, cyclin D2, cyclin E, survivin, XIAP, c-IAP2 and phospho-pRb. Butein also inhibited i) total and phospho-protein levels of IκB kinase (IKK)α and IKKβ, ii) degradation and phosphorylation of IκBα, iii) JunB and JunD, iv) total and phospho-protein levels of Akt, v) phosphorylation of RelA, vi) heat shock protein 90, and vii) DNA-binding activity of NF-κB and AP-1. In mice harboring ATLL xenograft tumors, butein caused a significant inhibition of tumor growth and reduced serum levels of soluble interleukin-2 receptor α chain and soluble cluster of differentiation 30. Considered together, the results indicated that butein has antiproliferative and proapoptotic properties through the suppression of NF-κB, AP-1 and Akt signaling in HTLV-1-infected T cells, both in vitro and in vivo, suggesting its therapeutic potential against HTLV-1-associated diseases including ATLL.
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August-2017
Volume 51 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Ishikawa C, Senba M and Mori N: Butein inhibits NF-κB, AP-1 and Akt activation in adult T-cell leukemia/lymphoma. Int J Oncol 51: 633-643, 2017
APA
Ishikawa, C., Senba, M., & Mori, N. (2017). Butein inhibits NF-κB, AP-1 and Akt activation in adult T-cell leukemia/lymphoma. International Journal of Oncology, 51, 633-643. https://doi.org/10.3892/ijo.2017.4026
MLA
Ishikawa, C., Senba, M., Mori, N."Butein inhibits NF-κB, AP-1 and Akt activation in adult T-cell leukemia/lymphoma". International Journal of Oncology 51.2 (2017): 633-643.
Chicago
Ishikawa, C., Senba, M., Mori, N."Butein inhibits NF-κB, AP-1 and Akt activation in adult T-cell leukemia/lymphoma". International Journal of Oncology 51, no. 2 (2017): 633-643. https://doi.org/10.3892/ijo.2017.4026