Inhibition of intrinsic protein tyrosine kinase activity of EGF-receptor kinase complex from human breast cancer cells by the marine sponge metabolite (+)-aeroplysinin-1.
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.
Kreuter
M H
MH
Abteilung Angewandte Molekularbiologie, Universität, Mainz, FRG.
Leake
R E
RE
Rinaldi
F
F
Müller-Klieser
W
W
Maidhof
A
A
Müller
W E
WE
Schröder
H C
HC
D000097:Acetonitriles / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000201:enzymology*; D002118:Calcium / Q000378:metabolism; D002455:Cell Division; D053138:Cyclohexenes; D004305:Dose-Response Relationship, Drug; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D051379:Mice; D010766:Phosphorylation; D011161:Porifera; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D013379:Substrate Specificity; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000097:Acetonitriles; D053138:Cyclohexenes; C001569:aeroplysinin; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D002118:Calcium