The anticancer prodrugs of butyric acid AN-7 and AN-9, possess antiangiogenic properties

Cancer Lett. 2007 Oct 18;256(1):39-48. doi: 10.1016/j.canlet.2007.05.011. Epub 2007 Jul 3.

Abstract

The antiangiogenic and antineoplastic activities of the butyric acid prodrugs AN-7 and AN-9 were demonstrated in vitro with HUVEC by inhibition of proliferation and vascular tubes formation, enhanced apoptosis, and inhibition of 22Rv-1 cells migration. In the sc implanted human prostate tumors (22Rv-1) in nude mice, AN-7 significantly inhibited Ki-67, HIF-1alpha, HER-2/neu, bFGF and increased PTEN level. AN-7 and AN-9 reduced hemoglobin accumulation in matrigel plugs implanted sc in Balb-c mice. Herein, we show that the anticancer activity of AN-7 and AN-9 can be attributed in part to their antiangiogenic activities suggesting potential therapeutic benefits for prostate cancer patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Butyrates / pharmacology*
  • Cell Proliferation / drug effects
  • Endothelium, Vascular / drug effects
  • Fibroblast Growth Factor 2 / genetics
  • Fibroblast Growth Factor 2 / metabolism
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Ki-67 Antigen / genetics
  • Ki-67 Antigen / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neovascularization, Pathologic / drug therapy*
  • Organophosphorus Compounds / pharmacology*
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism
  • Prodrugs / pharmacology*
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism
  • Tumor Cells, Cultured
  • Umbilical Veins / cytology

Substances

  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Butyrates
  • Hif1a protein, mouse
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Ki-67 Antigen
  • Organophosphorus Compounds
  • Prodrugs
  • diethoxyphosphoryloxymethyl butanoate
  • Fibroblast Growth Factor 2
  • pivalyloxymethyl butyrate
  • Receptor, ErbB-2
  • PTEN Phosphohydrolase
  • Pten protein, mouse