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

doi:10.1016/j.canlet.2011.08.002

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

Research output: Contribution to journal › Article › peer-review

25 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 language	English
Pages (from-to)	91-100
Number of pages	10
Journal	Cancer Letters
Volume	312
Issue number	1
DOIs	https://doi.org/10.1016/j.canlet.2011.08.002
Publication status	Published - Dec 15 2011
Externally published	Yes

All Science Journal Classification (ASJC) codes

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.canlet.2011.08.002

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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

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

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

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.",

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

note = "Funding Information: The authors are grateful to Ms. Yoko Nakagawa for her excellent technical support. This work was supported in part by Grant-in-Aids for Scientific Research and the Global COE Program “Center for Frontier Medicine” from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan, and by Grants from the Yasuda Medical Foundation and the Fujiwara Memorial Foundation. ",

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doi = "10.1016/j.canlet.2011.08.002",

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AU - Nagao, Rina

AU - Ashihara, Eishi

AU - Kimura, Shinya

AU - Strovel, Jeffrey W.

AU - Yao, Hisayuki

AU - Takeuchi, Miki

AU - Tanaka, Ruriko

AU - Hayashi, Yoshihiro

AU - Hirai, Hideyo

AU - Padia, Janak

AU - Strand, Kathryn

AU - Maekawa, Taira

N1 - Funding Information: The authors are grateful to Ms. Yoko Nakagawa for her excellent technical support. This work was supported in part by Grant-in-Aids for Scientific Research and the Global COE Program “Center for Frontier Medicine” from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan, and by Grants from the Yasuda Medical Foundation and the Fujiwara Memorial Foundation.

PY - 2011/12/15

Y1 - 2011/12/15

N2 - 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.

AB - 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.

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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

Abstract

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UN SDGs

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