Captopril inhibits glioma cell invasion in vitro: involvement of matrix metalloproteinases.
We investigated the effects of captopril on the activity of matrix metalloproteinases (MMPs) secreted by T98G glioma cells and their invasiveness in vitro. On gelatin zymography, captopril inhibited gelatinolytic activities in the culture media of T98G cells. This inhibitory effect was reversed by the presence of excess zinc. In an in vitro invasion assay, invasion into the reconstituted basement membrane (Matrigel) by T98G glioma cells was inhibited by captopril in a dose-dependent manner. This inhibitory effect was also reversed by the addition of zinc to the culture media. However, at the effective concentration of captopril for the prevention of tumor cell invasion it did not inhibit the motility, adhesion to Matrigel or proliferation of T98G cells. These findings suggest that captopril inhibits the invasiveness of T98G glioma cells due to its MMP inhibitory activity, chelating zinc ions at the active center of MMPs.
Nakagawa
T
T
Department of Neurosurgery, Fukui Medical School, Japan.
Kubota
T
T
Kabuto
M
M
Kodera
T
T
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D002216:Captopril / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018093:Gelatinases / Q000037:antagonists & inhibitors* / Q000502:physiology; D005910:Glioma / Q000188:drug therapy / Q000473:pathology*; D006801:Humans; D009361:Neoplasm Invasiveness; D014407:Tumor Cells, Cultured; D015032:Zinc / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D002216:Captopril; D018093:Gelatinases; D015032:Zinc