31 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)7031-7039
Number of pages9
JournalJournal of Agricultural and Food Chemistry
Volume60
Issue number28
DOIs
Publication statusPublished - Jul 18 2012

Fingerprint

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

Keywords

  • β-catenin
  • imatinib resistance
  • leukemia stem cells
  • reactive oxygen species
  • sulforaphane

ASJC Scopus subject areas

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

Cite this

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.

In: Journal of Agricultural and Food Chemistry, Vol. 60, No. 28, 18.07.2012, p. 7031-7039.

Research output: Contribution to journalArticle

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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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