Sulforaphane potentiates the efficacy of imatinib against chronic leukemia cancer stem cells through enhanced abrogation of Wnt/β-catenin function

Li Ching Lin, Chi-Tai Yeh, Chia Chun Kuo, Chi-Ming Lee, Gow Chin Yen, Liang Shun Wang, Chih Hsiung Wu, Wei Chung Vivian Yang, Alexander T H Wu

研究成果: 雜誌貢獻文章

31 引文 (Scopus)

摘要

Sulforaphane (SFN) has been indicated for the prevention and suppression of tumorigenesis in solid tumors. Herein, we evaluated SFN's effects on imatinib (IM)-resistant leukemia stem cells (LSCs). CD34+/CD38- and CD34+/CD38+ LSCs were isolated from KU812 cell line flowcytometrically. Isolated LSCs showed high expression of Oct4, CD133, β-catenin, and Sox2 and IM resistance. Differentially, CD34 +/CD38- LSCs demonstrated higher BCR-ABL and β-catenin expression and imatinib (IM) resistance than CD34 +/CD38+ counterparts. IM and SFN combined treatment sensitized CD34+/CD38- LSCs and induced apoptosis, shown by increased caspase 3, PARP, and Bax while decreased Bcl-2 expression. Additionally, the combined treatment reduced BCR-ABL and β-catenin and MDR-1 protein expression. Mechanistically, IM and SFN combined treatment resensitized LSCs by inducing intracellular reactive oxygen species (ROS). Importantly, β-catenin-silenced LSCs exhibited reduced glutathione S-transferase pi 1 (GSTP1) expression and intracellular GSH level, which led to increased sensitivity toward IM and SFN. We demonstrated that IM and SFN combined treatment effectively eliminated CD34+/CD38- LSCs. Since SFN has been shown well tolerated in both animals and human, this regimen could be considered for clinical trials.
原文英語
頁(從 - 到)7031-7039
頁數9
期刊Journal of Agricultural and Food Chemistry
60
發行號28
DOIs
出版狀態已發佈 - 七月 18 2012

指紋

Catenins
Neoplastic Stem Cells
Stem cells
leukemia
stem cells
Leukemia
Stem Cells
Glutathione S-Transferase pi
Imatinib Mesylate
sulforafan
neoplasm cells
caspase-3
glutathione transferase
Caspase 3
carcinogenesis
Glutathione
Tumors
reactive oxygen species
clinical trials
Reactive Oxygen Species

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Chemistry(all)

引用此文

Sulforaphane potentiates the efficacy of imatinib against chronic leukemia cancer stem cells through enhanced abrogation of Wnt/β-catenin function. / Lin, Li Ching; Yeh, Chi-Tai; Kuo, Chia Chun; Lee, Chi-Ming; Yen, Gow Chin; Wang, Liang Shun; Wu, Chih Hsiung; Yang, Wei Chung Vivian; Wu, Alexander T H.

於: Journal of Agricultural and Food Chemistry, 卷 60, 編號 28, 18.07.2012, p. 7031-7039.

研究成果: 雜誌貢獻文章

Lin, Li Ching ; Yeh, Chi-Tai ; Kuo, Chia Chun ; Lee, Chi-Ming ; Yen, Gow Chin ; Wang, Liang Shun ; Wu, Chih Hsiung ; Yang, Wei Chung Vivian ; Wu, Alexander T H. / Sulforaphane potentiates the efficacy of imatinib against chronic leukemia cancer stem cells through enhanced abrogation of Wnt/β-catenin function. 於: Journal of Agricultural and Food Chemistry. 2012 ; 卷 60, 編號 28. 頁 7031-7039.
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abstract = "Sulforaphane (SFN) has been indicated for the prevention and suppression of tumorigenesis in solid tumors. Herein, we evaluated SFN's effects on imatinib (IM)-resistant leukemia stem cells (LSCs). CD34+/CD38- and CD34+/CD38+ LSCs were isolated from KU812 cell line flowcytometrically. Isolated LSCs showed high expression of Oct4, CD133, β-catenin, and Sox2 and IM resistance. Differentially, CD34 +/CD38- LSCs demonstrated higher BCR-ABL and β-catenin expression and imatinib (IM) resistance than CD34 +/CD38+ counterparts. IM and SFN combined treatment sensitized CD34+/CD38- LSCs and induced apoptosis, shown by increased caspase 3, PARP, and Bax while decreased Bcl-2 expression. Additionally, the combined treatment reduced BCR-ABL and β-catenin and MDR-1 protein expression. Mechanistically, IM and SFN combined treatment resensitized LSCs by inducing intracellular reactive oxygen species (ROS). Importantly, β-catenin-silenced LSCs exhibited reduced glutathione S-transferase pi 1 (GSTP1) expression and intracellular GSH level, which led to increased sensitivity toward IM and SFN. We demonstrated that IM and SFN combined treatment effectively eliminated CD34+/CD38- LSCs. Since SFN has been shown well tolerated in both animals and human, this regimen could be considered for clinical trials.",
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T1 - Sulforaphane potentiates the efficacy of imatinib against chronic leukemia cancer stem cells through enhanced abrogation of Wnt/β-catenin function

AU - Lin, Li Ching

AU - Yeh, Chi-Tai

AU - Kuo, Chia Chun

AU - Lee, Chi-Ming

AU - Yen, Gow Chin

AU - Wang, Liang Shun

AU - Wu, Chih Hsiung

AU - Yang, Wei Chung Vivian

AU - Wu, Alexander T H

PY - 2012/7/18

Y1 - 2012/7/18

N2 - Sulforaphane (SFN) has been indicated for the prevention and suppression of tumorigenesis in solid tumors. Herein, we evaluated SFN's effects on imatinib (IM)-resistant leukemia stem cells (LSCs). CD34+/CD38- and CD34+/CD38+ LSCs were isolated from KU812 cell line flowcytometrically. Isolated LSCs showed high expression of Oct4, CD133, β-catenin, and Sox2 and IM resistance. Differentially, CD34 +/CD38- LSCs demonstrated higher BCR-ABL and β-catenin expression and imatinib (IM) resistance than CD34 +/CD38+ counterparts. IM and SFN combined treatment sensitized CD34+/CD38- LSCs and induced apoptosis, shown by increased caspase 3, PARP, and Bax while decreased Bcl-2 expression. Additionally, the combined treatment reduced BCR-ABL and β-catenin and MDR-1 protein expression. Mechanistically, IM and SFN combined treatment resensitized LSCs by inducing intracellular reactive oxygen species (ROS). Importantly, β-catenin-silenced LSCs exhibited reduced glutathione S-transferase pi 1 (GSTP1) expression and intracellular GSH level, which led to increased sensitivity toward IM and SFN. We demonstrated that IM and SFN combined treatment effectively eliminated CD34+/CD38- LSCs. Since SFN has been shown well tolerated in both animals and human, this regimen could be considered for clinical trials.

AB - Sulforaphane (SFN) has been indicated for the prevention and suppression of tumorigenesis in solid tumors. Herein, we evaluated SFN's effects on imatinib (IM)-resistant leukemia stem cells (LSCs). CD34+/CD38- and CD34+/CD38+ LSCs were isolated from KU812 cell line flowcytometrically. Isolated LSCs showed high expression of Oct4, CD133, β-catenin, and Sox2 and IM resistance. Differentially, CD34 +/CD38- LSCs demonstrated higher BCR-ABL and β-catenin expression and imatinib (IM) resistance than CD34 +/CD38+ counterparts. IM and SFN combined treatment sensitized CD34+/CD38- LSCs and induced apoptosis, shown by increased caspase 3, PARP, and Bax while decreased Bcl-2 expression. Additionally, the combined treatment reduced BCR-ABL and β-catenin and MDR-1 protein expression. Mechanistically, IM and SFN combined treatment resensitized LSCs by inducing intracellular reactive oxygen species (ROS). Importantly, β-catenin-silenced LSCs exhibited reduced glutathione S-transferase pi 1 (GSTP1) expression and intracellular GSH level, which led to increased sensitivity toward IM and SFN. We demonstrated that IM and SFN combined treatment effectively eliminated CD34+/CD38- LSCs. Since SFN has been shown well tolerated in both animals and human, this regimen could be considered for clinical trials.

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KW - leukemia stem cells

KW - reactive oxygen species

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