| Autor: |
Wood DL; Cardiovascular Research, Lilly Research Laboratories, Indianapolis, Indiana 46285, USA., Panda D, Wiernicki TR, Wilson L, Jordan MA, Singh JP |
| Jazyk: |
angličtina |
| Zdroj: |
Molecular pharmacology [Mol Pharmacol] 1997 Sep; Vol. 52 (3), pp. 437-44. |
| DOI: |
10.1124/mol.52.3.437 |
| Abstrakt: |
The mechanism of action of a novel antiproliferative compound LY290181 [2-amino-4-(3-pyridyl)-4H-naphtho(1,2-b)pyran-3-carbonitrile] was characterized. LY290181 is a potent inhibitor of cell proliferation, producing 50% inhibition of vascular smooth muscle, endothelial, Chinese hamster ovary, HeLa, and human erythroleukemia cells at concentrations of 8-40 nM. Cell cycle analysis showed that LY290181 caused accumulation of smooth muscle cells at the G2/M phase and induced mitotic arrest in Chinese hamster ovary cells and HeLa cells. At low concentrations (3-30 nM), LY290181 blocked transition of cells from metaphase to anaphase and disrupted mitotic spindle organization. At high concentrations (>/=100 nM), LY290181 produced a concentration-dependent loss of cytoplasmic and spindle microtubules. LY290181 inhibited the polymerization of purified bovine brain microtubule protein into microtubules, and it depolymerized preformed microtubules. Using tubulin-1-anilino-8-naphthalene sulfonate complex fluorescence, we have shown that LY290181 directly interacted with tubulin in a unique manner. These studies show that LY290181 induces cell growth arrest in prometaphase/metaphase, and tubulin appears to be its molecular target. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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