The angiogenesis inhibitor NM-3 is active against human NSCLC xenografts alone and in combination with docetaxel

Cancer Chemother Pharmacol. 2005 Dec;56(6):610-4. doi: 10.1007/s00280-005-1013-4. Epub 2005 Jun 10.

Abstract

The novel isocoumarin 2-(8-hydroxy-6-methoxy-1-oxo-1 H-2-benzopyran-3-yl) propionic acid (NM-3) has completed phase I clinical evaluation as an orally bioavailable angiogenesis inhibitor. NM-3 directly kills both endothelial and tumor cells in vitro at low mM concentrations and is effective in the treatment of diverse human tumor xenografts in mice. The present work has assessed the activity of NM-3 against human non-small-cell lung cancer (NSCLC) cells when used alone and in combination with docetaxel. The results demonstrate that NM-3 decreases clonogenic survival of NSCLC cells at clinically achievable concentrations. The results also demonstrate that NM-3 is effective in the treatment of NSCLC (A549, NCI-H460) tumor xenografts in mice. Moreover, NM-3 potentiated the antitumor activity of docetaxel against NSCLC xenografts without increasing toxicity. Our findings indicate that NM-3 may be effective alone or in combination with docetaxel in the treatment of patients with NSCLC.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Angiogenesis Inhibitors / pharmacology
  • Angiogenesis Inhibitors / therapeutic use*
  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor / drug effects
  • Cell Line, Tumor / pathology
  • Cell Survival / drug effects
  • Docetaxel
  • Drug Screening Assays, Antitumor
  • Humans
  • Isocoumarins / pharmacology
  • Isocoumarins / therapeutic use*
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Mice
  • Mice, Nude
  • Neoplasms, Experimental / drug therapy
  • Neoplasms, Experimental / pathology
  • Taxoids / pharmacology
  • Taxoids / therapeutic use*

Substances

  • Angiogenesis Inhibitors
  • Antineoplastic Agents, Phytogenic
  • Isocoumarins
  • Taxoids
  • isocoumarin NM-3
  • Docetaxel