Curcumin disrupts meiotic and mitotic divisions via spindle impairment and inhibition of CDK1 activity.

Abstract:

OBJECTIVES:Curcumin, a natural compound, is a potent anti-cancer agent, which inhibits cell division and/or induces cell death. It is believed that normal cells are less sensitive to curcumin than malignant cells; however, the mechanism(s) responsible for curcumin's effect on normal cells are poorly understood. The aim of this study was to verify the hypothesis that curcumin affects normal cell division by influencing microtubule stability, using mouse oocyte and early embryo model systems. MATERIALS AND METHODS:Maturating mouse oocytes and two-cell embryos were treated with different concentrations of curcumin (10-50 microm), and meiotic resumption and mitotic cleavage were analysed. Spindle and chromatin structure were visualized using confocal microscopy. In addition, acetylation and in vitro polymerization of tubulin, in the presence of curcumin, were investigated and the damage to double-stranded DNA was studied using gammaH2A.X. CDK1 activity was measured. RESULTS AND CONCLUSIONS:We have shown for the first time, that curcumin, in a dose-dependent manner, delays and partially inhibits meiotic resumption of oocytes and inhibits meiotic and mitotic divisions by causing disruption of spindle structure and does not induce DNA damage. Our analysis indicated that curcumin affects CDK1 kinase activity but does not directly affect microtubule polymerization and tubulin acetylation. As our study showed that curcumin impairs generative and somatic cell division, its future clinical use or of its derivatives with improved bioavailability after oral administration, should take into consideration the possibility of extensive side-effects on normal cells.

journal_name

Cell Prolif

journal_title

Cell proliferation

authors

Bielak-Zmijewska A,Sikora-Polaczek M,Nieznanski K,Mosieniak G,Kolano A,Maleszewski M,Styrna J,Sikora E

doi

10.1111/j.1365-2184.2010.00684.x

subject

Has Abstract

pub_date

2010-08-01 00:00:00

pages

354-64

issue

4

eissn

0960-7722

issn

1365-2184

pii

CPR684

journal_volume

43

pub_type

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