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.
ASJC Scopus subject areas
- Agricultural and Biological Sciences(all)
Lin, L. C., Yeh, C-T., Kuo, C. C., Lee, C-M., Yen, G. C., Wang, L. S., Wu, C. H., Yang, W. C. V., & Wu, A. T. H. (2012). Sulforaphane potentiates the efficacy of imatinib against chronic leukemia cancer stem cells through enhanced abrogation of Wnt/β-catenin function. Journal of Agricultural and Food Chemistry, 60(28), 7031-7039. https://doi.org/10.1021/jf301981n