Dual inhibition of Bcr-Abl and Hsp90 by C086 potently inhibits the proliferation of imatinib-resistant CML cells.

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Abstract

Although tyrosine kinase inhibitors (TKI) such as imatinib provide an effective treatment against Bcr-Abl kinase activity in the mature cells of patients with chronic myelogenous leukemia (CML), TKIs probably cannot eradicate the leukemia stem cell (LSC) population. Therefore, alternative therapies are required to target both mature CML cells with wild-type (WT) or mutant Bcr-Abl and LSCs. To investigate the effect of C086, a derivative of curcumin, on imatinib-resistant cells, we explored its underlying mechanisms of Bcr-Abl kinase and heat shock protein 90 (Hsp90) function inhibition.

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Author and article information

Journal

Journal ID (iso-abbrev): Clin. Cancer Res.

Title: Clinical cancer research : an official journal of the American Association for Cancer Research

Publisher: American Association for Cancer Research (AACR)

ISSN: 1078-0432

ISSN (Print): 1078-0432

Publication date (Electronic): Feb 15 2015

Volume: 21

Issue: 4

Affiliations

[1 ] Department of Pharmacology, School of Pharmacy, Fujian Medical University (FMU), Fuzhou, P.R. China. Institute of Materia Medica, Fujian Medical University (FMU), Fuzhou, P.R. China. Fuijan Key Laboratory of Natural Medicine Pharmacology, Fujian Medical University (FMU), Fuzhou, P. R. China. wlx-lisa@126.com chenyz@mail.fjmu.edu.cn xjh@mail.fjmu.edu.cn.

[2 ] Department of Pathology, School of Basic Medicine, Fujian Medical University (FMU), Fuzhou, P.R. China.

[3 ] Department of Pharmacology, School of Pharmacy, Fujian Medical University (FMU), Fuzhou, P.R. China. Institute of Materia Medica, Fujian Medical University (FMU), Fuzhou, P.R. China.

[4 ] Institute of Materia Medica, Fujian Medical University (FMU), Fuzhou, P.R. China. Fuijan Key Laboratory of Natural Medicine Pharmacology, Fujian Medical University (FMU), Fuzhou, P. R. China. Department of Pharmacochemistry, School of Pharmacy, Fujian Medical University (FMU), Fuzhou, P.R. China.

[5 ] Shanghai Institute of Materia Medica, P.R. China.

[6 ] Institute of Materia Medica, Fujian Medical University (FMU), Fuzhou, P.R. China. Fuijan Key Laboratory of Natural Medicine Pharmacology, Fujian Medical University (FMU), Fuzhou, P. R. China.

[7 ] Department of Pharmacology, School of Pharmacy, Fujian Medical University (FMU), Fuzhou, P.R. China.

[8 ] Institute of Materia Medica, Fujian Medical University (FMU), Fuzhou, P.R. China.

[9 ] Fujian Institute of Hematology, Union Hospital, Fujian Medical University (FMU), Fuzhou, P. R. China.

[10 ] Fujian Institute of Hematology, Union Hospital, Fujian Medical University (FMU), Fuzhou, P. R. China. wlx-lisa@126.com chenyz@mail.fjmu.edu.cn xjh@mail.fjmu.edu.cn.

Article

Publisher Item ID: 1078-0432.CCR-13-3317

DOI: 10.1158/1078-0432.CCR-13-3317

PubMed ID: 25501124

SO-VID: f4fa7e30-5730-42df-bf7d-929964c7e32d

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