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

Bielak-Żmijewska, Anna; Sikora-Polaczek, Marta; Nieznañski, Krzysztof; Mosieniak, Grażyna; Kolano, Agnieszka; Maleszewski, Marek; Styrna, Józefa; Sikora, Ewa

doi:10.1111/j.1365-2184.2010.00684.x

Cited by 21 publications

(14 citation statements)

References 62 publications

(92 reference statements)

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“…It has been observed in cells undergoing prolonged mitosis that the proteins protecting telomeres were dispersed which provoked senescence induction (Hayashi et al 2012 ). We have shown earlier that curcumin caused a mitotic spindle dysfunction by its impact on microtubules (Bielak-Zmijewska et al 2010 ), and this could be the reason of a prolonged mitotic arrest and telomere proteins diffusion. However, on the basis of the current results, we can exclude that curcumin induced senescence in VSMCs and ECs by mitosis prolongation.…”

Section: Discussionmentioning

confidence: 90%

Curcumin induces senescence of primary human cells building the vasculature in a DNA damage and ATM-independent manner

Grabowska

Kucharewicz

Wnuk

et al. 2015

AGE

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Curcumin is considered not only as a supplement of the diet but also as a drug in many types of diseases and even as a potential anti-aging compound. It can reduce inflammation that increases with age and accompanies almost all age-related diseases. It has been suggested that curcumin can play a beneficial role in the cardiovascular system. However, there are also data showing that curcumin can induce senescence in cancer cells, which is a beneficial effect in cancer therapy but an undesirable one in the case of normal cells. It is believed that cellular senescence accompanies age-related changes in the cardiovascular system. The aim of this study was to check if curcumin, in a certain range of concentrations, can induce senescence in cells building the vasculature. We have found that human vascular smooth muscle and endothelial cells derived from aorta are very sensitive to curcumin treatment and can senesce upon treatment with cytostatic doses. We observed characteristic senescence markers but the number of DNA damage foci decreased. Surprisingly, in vascular smooth muscle cell (VSMC) activation of DNA damage response pathway downstream of ataxia-telangiectasia mutated (ATM) was observed. ATM silencing and the supplementation of antioxidants, N-acetyl-L-cysteine (NAC) or trolox, did not reduce the number of senescent cells. Thus, we have shown that curcumin can induce senescence of cells building the vasculature, which is DNA damage and ATM independent and is not induced by increased reactive oxygen species (ROS) level. We postulate that an increase in the bioavailability of curcumin should be introduced very carefully considering senescence induction as a side effect.Electronic supplementary materialThe online version of this article (doi:10.1007/s11357-014-9744-y) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 90%

Curcumin induces senescence of primary human cells building the vasculature in a DNA damage and ATM-independent manner

Grabowska

Kucharewicz

Wnuk

et al. 2015

AGE

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“…It is believed that they are more sensitive to curcumin than normal cells (14). However, we have shown that curcumin-induced cell death also occurs in normal cells (5)(6)(7), but the mechanism of cell death in normal resting cells is still elusive.…”

Section: Introductionmentioning

confidence: 94%

“…Curcumin has been shown to inhibit proliferation and to induce cell death in various cancer cells (2). Also our group has shown that curcumin is able to induce cell death in many different cancer cell lines (4)(5)(6)(7)(8)(9)(10)(11)(12)(13). It is believed that they are more sensitive to curcumin than normal cells (14).…”

Section: Introductionmentioning

confidence: 96%

DNA damage-independent apoptosis induced by curcumin in normal resting human T cells and leukaemic Jurkat cells

Korwek¹,

Bielak-Żmijewska²,

Mosieniak³

et al. 2013

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Curcumin, a phytochemical derived from the rhizome of Curcuma longa, is a very potent inducer of cancer cell death. It is believed that cancer cells are more sensitive to curcumin treatment than normal cells. Curcumin has been shown to act as a prooxidant and induce DNA lesions in normal cells. We were interested in whether curcumin induces DNA damage and the DNA damage response (DDR) signalling pathway leading to apoptosis in normal resting human T cells. To this end, we analysed DNA damage after curcumin treatment of resting human T cells (CD3(+)) and of proliferating leukaemic Jurkat cells by the fluorimetric detection of alkaline DNA unwinding (FADU) assay and immunocytochemical detection of γ-H2AX foci. We showed that curcumin-treated Jurkat cells and resting T cells showed neither DNA lesions nor did they activate key proteins in the DDR signalling pathway, such as phospho-ATM and phospho-p53. However, both types of cell were equally sensitive to curcumin-induced apoptosis and displayed activation of caspase-8 but not of DNA damage-dependent caspase-2. Altogether, our results revealed that curcumin can induce apoptosis of normal resting human T cells that is not connected with DNA damage.

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“…28, 29, 30 The apoptotic process seems to be initiated by DNA damage triggered by TOP2 poisoning. 31, 32 Despite the possible side effects of Curcumin on fertility and immune functions, 33, 34, 35 in the majority of normal and primary cells, it does not elicit a cytotoxic response.…”

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confidence: 99%

Concurrent inhibition of enzymatic activity and NF-Y-mediated transcription of Topoisomerase-IIα by bis-DemethoxyCurcumin in cancer cells

et al. 2013

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Topoisomerases-IIα (TOP2A) enzyme is essential for cell viability due to its fundamental role in DNA metabolism and in chromatin organization during interphase and mitosis. TOP2A expression is finely regulated at the transcriptional level through the binding of the CCAAT-transcription factor NF-Y to its promoter. Overexpression and/or amplification of TOP2A have been observed in many types of cancers. For this reason, TOP2A is the target of the most widely successful drugs in cancer chemotherapy, such as TOP2A poisons, which stabilize TOP2A-DNA cleavage complexes and create DSBs, leading to chromosome damage and cell death. We previously reported that the Curcumin-derivative bis-DemethoxyCurcumin (bDMC) is an anti-proliferative agent that inhibits cell growth by concomitant G1/S and G2/M arrest. Here we showed that bDMC irreversibly induces DSBs in cancer cells, but not in normal cells, by targeting TOP2A activity and expression. TOP2A ablation by siRNA corroborates its contribution to apoptosis induced by bDMC. Short-term exposure to bDMC induces retention of TOP2A-DNA intermediates, while longer exposure inhibits TOP2A transcription by affecting expression and sub-cellular localization of NF-Y subunits. ChIP analysis highlighted reduced recruitment of NF-Y to TOP2A regulatory regions, concomitantly to histone deacetylation and decreased gene transcription. Our findings suggest that the dual activity of bDMC on TOP2A represents a novel therapeutic strategy to induce persistent apoptosis in cancer cells and identify NF-Y regulation as a promising approach in anti-cancer therapy.

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

Cited by 21 publications

References 62 publications

Curcumin induces senescence of primary human cells building the vasculature in a DNA damage and ATM-independent manner

Curcumin induces senescence of primary human cells building the vasculature in a DNA damage and ATM-independent manner

DNA damage-independent apoptosis induced by curcumin in normal resting human T cells and leukaemic Jurkat cells

Concurrent inhibition of enzymatic activity and NF-Y-mediated transcription of Topoisomerase-IIα by bis-DemethoxyCurcumin in cancer cells

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