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Drug-induced
apoptosis by a matrix metalloproteinase inhibitor, SI-27 on human malignant
glioma cell lines; in vitro study
Ryuzaburo Kanazawa, Daizo
Yoshida, Hiroshi Takahashi, Yuichi Sugisaki, Satoru Suzuki and Akira Teramoto
Department of Neurosurgery
(R.K., D.Y., H.T., A.T.), Central Institute for Electron Microscopic Researches
(Y.S.), Department of Biochemistry and
Molecular Biology (S.S.), Nippon Medical School, Tokyo, Japan
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.
Key words: apoptosis,
caspase, malignant glioma, matrix metalloproteinase, SI-27
© 2004 Kluwer Academic
Publishers. Printed in the Netherlands.
Source: http://journals.kluweronline.com/article.asp?PIPS=5146807
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