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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21 Citations (Scopus)

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

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Nagao, R., Ashihara, E., Kimura, S., Strovel, J. W., 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, 312(1), 91-100. https://doi.org/10.1016/j.canlet.2011.08.002