Angiogenesis inhibitor TNP-470 inhibits growth and metastasis of a hormone-independent rat prostatic carcinoma cell line

J Urol. 1998 Jul;160(1):210-3.

Abstract

Purpose: Inhibitory effects of TNP-470, a synthetic analogue of the antibiotic fumagillin secreted by Aspergillus fumigatus, were studied with respect to growth and lung metastasis of the hormone-independent rat prostatic carcinoma cell line AT6.3.

Materials and methods: Rat prostatic carcinoma AT6.3 cells were implanted in nude mice subcutaneously. Antimetastatic and growth-inhibitory effects of TNP-470 in vivo were examined 3 weeks after inoculation of AT6.3 cells. Direct growth-inhibitory effect was examined by MTT assay in vitro.

Results: TNP-470 inhibited the growth of AT6.3 cells in vitro. Subcutaneously injected TNP-470 markedly reduced numbers and individual size of lung metastases from AT6.3 cells inoculated percutaneously or intravenously into male BALB/c-nu/nu mice.

Conclusion: This agent, which acts as an angiogenesis inhibitor, may prove to be clinically useful in preventing metastasis of hormone-independent prostatic cancer.

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / pharmacology*
  • Cell Division / drug effects
  • Cyclohexanes
  • Lung Neoplasms / prevention & control*
  • Lung Neoplasms / secondary*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Neovascularization, Pathologic / prevention & control*
  • O-(Chloroacetylcarbamoyl)fumagillol
  • Prostatic Neoplasms / blood supply
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / pathology*
  • Rats
  • Sesquiterpenes / pharmacology*
  • Tumor Cells, Cultured / drug effects

Substances

  • Antibiotics, Antineoplastic
  • Cyclohexanes
  • Sesquiterpenes
  • O-(Chloroacetylcarbamoyl)fumagillol