Anti-tumor effect of N-beta-alanyl-5-S-glutathionyldihydroxyphenylalanine (5-S-GAD), a novel anti-bacterial substance from an insect

Anticancer Res. 2000 Jan-Feb;20(1A):357-62.

Abstract

Purpose: We examined the anti-tumor effect of 5-S-GAD, a novel potent inhibitor of protein tyrosine kinases, isolated from the flesh fly in order to investigate the potential use of this compound as an anti-tumor agent.

Methods: In vitro growth inhibition was evaluated using the alamarBlue assay kit. In vivo anti-tumor activity was evaluated by i.p. treatment of 5-S-GAD against xenografted melanoma (LOX-IMV1) and breast carcinoma (MDA-MB-435S) in nude mice.

Results: Of 38 human cancer cell lines examined, this compound showed significant cytotoxicity toward two estrogen-negative breast carcinomas (MDA-MB-231 and MDA-MB-435S) and one malignant melanoma (LOX-IMV1) in vitro, indicating that it exhibits selective cytotoxicity to certain tumor cell lines. In accordance with its in vitro anti-tumor effect, 5-S-GAD was shown to significantly repress the growth of sensitive tumor cells in nude mice.

Conclusion: These results indicate that 5-S-GAD is potentially useful to treat certain human cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Benzoquinones
  • Breast Neoplasms / pathology*
  • Dihydroxyphenylalanine / analogs & derivatives*
  • Dihydroxyphenylalanine / pharmacology
  • Dihydroxyphenylalanine / therapeutic use
  • Diptera / chemistry*
  • Drug Screening Assays, Antitumor
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use
  • Female
  • Glutathione / analogs & derivatives*
  • Glutathione / pharmacology
  • Glutathione / therapeutic use
  • Humans
  • Lactams, Macrocyclic
  • Mammary Neoplasms, Experimental / drug therapy*
  • Melanoma / pathology*
  • Melanoma, Experimental / drug therapy*
  • Mice
  • Mice, Nude
  • Molecular Structure
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Transplantation
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Quinones / pharmacology
  • Rifabutin / analogs & derivatives
  • Transplantation, Heterologous
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / transplantation

Substances

  • Antineoplastic Agents
  • Benzoquinones
  • Enzyme Inhibitors
  • Lactams, Macrocyclic
  • N-beta-alanyl-5-S-glutathionyl-3,4-dihydroxyphenylalanine
  • Neoplasm Proteins
  • Quinones
  • Rifabutin
  • Dihydroxyphenylalanine
  • herbimycin
  • Protein-Tyrosine Kinases
  • Glutathione