Inhibition of mitosis and microtubule function through direct tubulin binding by a novel antiproliferative naphthopyran LY290181

Dan L. Wood, Dulal Panda, Todd R. Wiernicki, Leslie Wilson, Mary Ann Jordan, Jai Pal Singh

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

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 celts 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.

Original languageEnglish (US)
Pages (from-to)437-444
Number of pages8
JournalMolecular Pharmacology
Volume52
Issue number3
StatePublished - Sep 1997
Externally publishedYes

Fingerprint

LY 290181
Tubulin
Mitosis
Microtubules
Metaphase
Cricetulus
Ovary
Prometaphase
Microtubule Proteins
Leukemia, Erythroblastic, Acute
Anaphase
Spindle Apparatus
G2 Phase

ASJC Scopus subject areas

  • Pharmacology

Cite this

Wood, D. L., Panda, D., Wiernicki, T. R., Wilson, L., Jordan, M. A., & Singh, J. P. (1997). Inhibition of mitosis and microtubule function through direct tubulin binding by a novel antiproliferative naphthopyran LY290181. Molecular Pharmacology, 52(3), 437-444.

Inhibition of mitosis and microtubule function through direct tubulin binding by a novel antiproliferative naphthopyran LY290181. / Wood, Dan L.; Panda, Dulal; Wiernicki, Todd R.; Wilson, Leslie; Jordan, Mary Ann; Singh, Jai Pal.

In: Molecular Pharmacology, Vol. 52, No. 3, 09.1997, p. 437-444.

Research output: Contribution to journalArticle

Wood, DL, Panda, D, Wiernicki, TR, Wilson, L, Jordan, MA & Singh, JP 1997, 'Inhibition of mitosis and microtubule function through direct tubulin binding by a novel antiproliferative naphthopyran LY290181', Molecular Pharmacology, vol. 52, no. 3, pp. 437-444.
Wood, Dan L. ; Panda, Dulal ; Wiernicki, Todd R. ; Wilson, Leslie ; Jordan, Mary Ann ; Singh, Jai Pal. / Inhibition of mitosis and microtubule function through direct tubulin binding by a novel antiproliferative naphthopyran LY290181. In: Molecular Pharmacology. 1997 ; Vol. 52, No. 3. pp. 437-444.
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