Growth inhibition of imatinib-resistant CML cells with the T315I mutation and hypoxia-adaptation by AV65 - a novel Wnt/β-catenin signaling inhibitor

Rina Nagao, Eishi Ashihara, Shinya Kimura, Jeffrey W. Strovel, Hisayuki Yao, Miki Takeuchi, Ruriko Tanaka, Yoshihiro Hayashi, Hideyo Hirai, Janak Padia, Kathryn Strand, Taira Maekawa

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Abstract

We investigated the effect of a novel Wnt/β-catenin signaling inhibitor, AV65 on imatinib mesylate (IM)-sensitive and -resistant human chronic myeloid leukemia (CML) cells in vitro. AV65 inhibited the proliferation of various CML cell lines including T315I mutation-harboring cells. AV65 reduced the expression of β-catenin in CML cells, resulting in the induction of apoptosis. Moreover, AV65 inhibited the proliferation of hypoxia-adapted primitive CML cells that overexpress β-catenin. The combination of AV65 with IM had a synergistic inhibitory effect on the proliferation of CML cells. These findings suggest that AV65 could be a novel therapeutic agent for the treatment of CML.

Original languageEnglish
Pages (from-to)91-100
Number of pages10
JournalCancer Letters
Volume312
Issue number1
DOIs
Publication statusPublished - Dec 15 2011

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Catenins
Myeloid Cells
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Mutation
Growth
Imatinib Mesylate
Hypoxia
Apoptosis
Cell Line

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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Growth inhibition of imatinib-resistant CML cells with the T315I mutation and hypoxia-adaptation by AV65 - a novel Wnt/β-catenin signaling inhibitor. / Nagao, Rina; Ashihara, Eishi; Kimura, Shinya; Strovel, Jeffrey W.; Yao, Hisayuki; Takeuchi, Miki; Tanaka, Ruriko; Hayashi, Yoshihiro; Hirai, Hideyo; Padia, Janak; Strand, Kathryn; Maekawa, Taira.

In: Cancer Letters, Vol. 312, No. 1, 15.12.2011, p. 91-100.

Research output: Contribution to journalArticle

Nagao, R, Ashihara, E, Kimura, S, Strovel, JW, Yao, H, Takeuchi, M, Tanaka, R, Hayashi, Y, Hirai, H, Padia, J, Strand, K & Maekawa, T 2011, 'Growth inhibition of imatinib-resistant CML cells with the T315I mutation and hypoxia-adaptation by AV65 - a novel Wnt/β-catenin signaling inhibitor', Cancer Letters, vol. 312, no. 1, pp. 91-100. https://doi.org/10.1016/j.canlet.2011.08.002
Nagao, Rina ; Ashihara, Eishi ; Kimura, Shinya ; Strovel, Jeffrey W. ; Yao, Hisayuki ; Takeuchi, Miki ; Tanaka, Ruriko ; Hayashi, Yoshihiro ; Hirai, Hideyo ; Padia, Janak ; Strand, Kathryn ; Maekawa, Taira. / Growth inhibition of imatinib-resistant CML cells with the T315I mutation and hypoxia-adaptation by AV65 - a novel Wnt/β-catenin signaling inhibitor. In: Cancer Letters. 2011 ; Vol. 312, No. 1. pp. 91-100.
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