Inhibition of intrinsic protein tyrosine kinase activity of EGF-receptor kinase complex from human breast cancer cells by the marine sponge metabolite (+)-aeroplysinin-1.

Abstract

1. (+)-Aeroplysinin-1, a naturally occurring tyrosine metabolite from the marine sponge Verongia aerophoba, was found to inhibit the phosphorylation of lipocortin-like proteins by a highly purified preparation of the epidermal growth factor (EGF) receptor-tyrosine protein kinase complex from MCF-7 breast carcinoma cells. 2. (+)-Aeroplysinin-1 blocked the EGF-dependent proliferation of both MCF-7 and ZR-75-1 human breast cancer cells and inhibited the ligand-induced endocytosis of the EGF receptor in vitro. 3. Treatment with aeroplysinin-1 in the concentration range at 0.25-0.5 microM resulted in a time- and dose-dependent total tumor cell death in vitro. 4. At a 10-fold higher concentration the compound did not reveal any cytostatic activity in normal human fibroblasts. 5. From these data we conclude that (+)-aeroplysinin-1 represents a compound which displays a strong anti-tumor effect on EGF-dependent tumor cell lines.

• Authors: M H Kreuter, R E Leake, F Rinaldi, W Müller-Klieser, A Maidhof, W E Müller, H C Schröder
• Journal: Comparative biochemistry and physiology. B, Comparative biochemistry (Comp Biochem Physiol B) Vol. 97 Issue 1 Pg. 151-8 ( 1990) ISSN: 0305-0491 [Print] England
• PMID: 2253475 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Acetonitriles
• Cyclohexenes
• aeroplysinin
• ErbB Receptors
• Protein-Tyrosine Kinases
• Calcium

Topics

• Acetonitriles (pharmacology)
• Animals
• Blotting, Western
• Breast Neoplasms (enzymology)
• Calcium (metabolism)
• Cell Division
• Cyclohexenes
• Dose-Response Relationship, Drug
• ErbB Receptors (metabolism)
• Humans
• Mice
• Phosphorylation
• Porifera
• Protein-Tyrosine Kinases (antagonists & inhibitors)
• Substrate Specificity
• Time Factors
• Tumor Cells, Cultured