Hammada scoparia flavonoids and rutin kill adherent and chemoresistant leukemic cells

Leuk Res. 2011 Aug;35(8):1093-101. doi: 10.1016/j.leukres.2010.12.011. Epub 2011 Jan 8.

Abstract

In search for compounds able to reduce cell adhesion-mediated drug resistance (CAM-DR), we studied effects of Hammada scoparia extracts on leukemic cells adherent or in suspension. We show that H. scoparia flavonoidic fraction and its compound rutin induce apoptosis specifically in adherent leukemic cells and abolish CAM-DR. Importantly, rutin inhibited survival of adherent leukemic progenitors (CD34(+)38(-)123(+)) but spared normal progenitors (CD34(+)38(-)). The pro-apoptotic effects of rutin were correlated with a decrease of active GSK3β and inhibitors of GSK3β reproduced rutin-induced cytotoxicity. This study uncovers the potential of H. scoparia flavonoids and rutin to overcome CAM-DR in acute myeloid leukemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD34 / metabolism
  • Apoptosis / drug effects*
  • Blotting, Western
  • Cell Adhesion / drug effects*
  • Cells, Cultured
  • Drug Resistance, Neoplasm / drug effects*
  • Flavonoids / pharmacology
  • Flow Cytometry
  • Glycogen Synthase Kinase 3 / antagonists & inhibitors
  • Glycogen Synthase Kinase 3 / metabolism
  • Glycogen Synthase Kinase 3 beta
  • Hematopoietic Stem Cells / drug effects
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / pathology*
  • Phytotherapy*
  • Rutin / pharmacology*
  • Scoparia / chemistry*
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Substances

  • Antigens, CD34
  • Flavonoids
  • Rutin
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Glycogen Synthase Kinase 3