Methyl-beta-cyclodextrin inhibits cell growth and cell cycle arrest via a prostaglandin E(2) independent pathway

Methyl-beta-cyclodextrin, a cyclic oligosaccharide known for its interaction with the plasma membrane induces several events in cells including cell growth and anti-tumor activity. In this study, we have investigated the possible role of cyclooxygenase 2 (COX-2) in cell growth arrest induced by meth...

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Published in:Experimental & molecular medicine 2004-02, Vol.36 (1), p.78-84
Main Authors: Choi, Young-Ae, Chin, Byung Rho, Rhee, Dong Hoon, Choi, Han-Gon, Chang, Hyeun-Wook, Kim, Jung-Hye, Baek, Suk-Hwan
Format: Article
Language:English
Subjects:
Animals
beta-Cyclodextrins - pharmacology
Cell Cycle - drug effects
Cell Cycle - physiology
Cell Line
Cell Proliferation - drug effects
Cyclooxygenase 2
Dinoprostone - metabolism
Dose-Response Relationship, Drug
Isoenzymes - genetics
Isoenzymes - metabolism
Macrophages - cytology
Macrophages - drug effects
Macrophages - physiology
Mice
Prostaglandin-Endoperoxide Synthases - genetics
Prostaglandin-Endoperoxide Synthases - metabolism
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Summary:Methyl-beta-cyclodextrin, a cyclic oligosaccharide known for its interaction with the plasma membrane induces several events in cells including cell growth and anti-tumor activity. In this study, we have investigated the possible role of cyclooxygenase 2 (COX-2) in cell growth arrest induced by methyl-beta-cyclodextrin in Raw264.7 macrophage cells. Methyl-beta-cyclodextrin inhibited cell growth and arrested the cell cycle, and this cell cycle arrest reduced the population of cells in the S phase, and concomitantly reduced cyclin A and D expressions. Methyl-beta-cyclodextrin in a dose- and time-dependent manner, also induced COX-2 expression, prostaglandin E(2) (PGE(2)) synthesis, and COX-2 promoter activity. Pretreatment of cells with NS398, a COX-2 specific inhibitor completely blocked PGE(2) synthesis induced by methyl-beta-cyclodextrin, however inhibition on cell proliferation and cell cycle arrest was not effected, suggesting non-association of COX-2 in the cell cycle arrest. These results suggest that methyl-beta-cyclodextrin induced cell growth inhibition and cell cycle arrest in Raw264.7 cells may be mediated by cyclin A and D1 expression.
ISSN:1226-3613
2092-6413
2092-6413
DOI:10.1038/emm.2004.11