Drug-induced apoptosis by a matrix metalloproteinase inhibitor, SI-27 on human malignant glioma cell lines; in vitro study.
Matrix metalloproteinase (MMP) plays important roles in cell invasion and tumor angiogenesis. SI-27, an anti-MMP agent, has already been shown to possess both in vitro anti-invasive and anti-angiogenic properties against malignant gliomas in non-cytotoxic dose concentrations. However, to the best of our knowledge, the molecular mechanism mediating the cytotoxic action by this agent and the molecular mechanism in the cytotoxic action against malignant glioma cell have not yet been clarified. Therefore, we assessed the effect in the cytotoxic dose concentrations to investigate whether this cytotoxic action is related to apoptosis in this study. The effect on human glioma cell lines (U87MG, U251MG, and U373MG) was examined by transmission electron microscope, agarose gel electrophoresis with the DNA fragmentation, flow cytometry with FITC-conjugated Annexin V, and detection of caspase activity. Drug-induced apoptosis was observed in the cytotoxic dose. The result indicated that the cytotoxity of SI-27 might be related to the drug-induced apoptosis mediated by caspase.
Kanazawa
Ryuzaburo
R
Department of Neurosurgery, Nippon Medical School, Tokyo, Japan. ryu@nms.ac.jp
Yoshida
Daizo
D
Takahashi
Hiroshi
H
Sugisaki
Yuichi
Y
Suzuki
Satoru
S
Teramoto
Akira
A
D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D004396:Coloring Agents; D004305:Dose-Response Relationship, Drug; D004587:Electrophoresis, Agar Gel; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D005434:Flow Cytometry; D005910:Glioma / Q000201:enzymology / Q000473:pathology*; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D008854:Microscopy, Electron; D009842:Oligopeptides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D013778:Tetrazolium Salts; D013844:Thiazoles
D004396:Coloring Agents; D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D009842:Oligopeptides; C421267:SI 27; D013778:Tetrazolium Salts; D013844:Thiazoles; D020169:Caspases; C022616:thiazolyl blue