Methyl-beta-cyclodextrin inhibits cell growth and cell cycle arrest via a prostaglandin E(2) independent pathway.
- Author:
Young Ae CHOI
1
;
Byung Rho CHIN
;
Dong Hoon RHEE
;
Han Gon CHOI
;
Hyeun Wook CHANG
;
Jung Hye KIM
;
Suk Hwan BAEK
Author Information
1. Department of Biochemistry and Molecular Biology, College of Medicine, Yeungnam University, Daegu 705-717, Korea. sbaek@med.yu.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
cyclin A;
cyclin D1;
cyclooxygenase-2;
methyl-beta-cyclodextrin
- MeSH:
Animals;
Cell Cycle/drug effects/*physiology;
Cell Line;
Cell Proliferation/*drug effects;
Dinoprostone/*metabolism;
Dose-Response Relationship, Drug;
Isoenzymes/genetics/*metabolism;
Macrophages/cytology/*drug effects/physiology;
Mice;
Prostaglandin-Endoperoxide Synthase/genetics/*metabolism;
Research Support, Non-U.S. Gov't;
beta-Cyclodextrins/*pharmacology
- From:Experimental & Molecular Medicine
2004;36(1):78-84
- CountryRepublic of Korea
- Language:English
-
Abstract:
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.
