AKT/NF-kappaB inhibitor xanthohumol targets cell growth and angiogenesis in hematologic malignancies

Cancer. 2007 Nov 1;110(9):2007-11. doi: 10.1002/cncr.23017.

Abstract

Background: Leukemias are dependent on Akt/NF-kappaB activation and angiogenesis.

Methods: The antiangiogenic Akt/NF-kappaB inhibitor xanthohumol (XN) has in vitro activity against acute and chronic myelogenous leukemia cell lines (AML, CML) and fresh samples from patients were investigated.

Results: Inhibition of cell proliferation is associated with induction of apoptosis and reduced VEGF secretion. Decreased cell invasion, metalloprotease production, and adhesion to endothelial cells observed in the presence of XN could prevent in vivo life-threatening complications of leukostasis and tissue infiltration.

Conclusions: As endothelial cells and hematopoietic cells are mutually correlated in their development and growth, targeting both tumor cells and endothelial cells with agents possessing cytotoxic and antiangiogenic activities may lead to synergistic antitumor effects interrupting a reciprocal stimulatory loop between leukemia and endothelial cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Blotting, Western
  • Cell Adhesion / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects*
  • Dose-Response Relationship, Drug
  • Flavonoids
  • Hematologic Neoplasms*
  • Humans
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / drug effects
  • Neovascularization, Pathologic / drug therapy*
  • Propiophenones / pharmacology*
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / drug effects

Substances

  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Flavonoids
  • NF-kappa B
  • Propiophenones
  • Proto-Oncogene Proteins c-akt
  • xanthohumol