Curcumin disrupts mitotic spindle structure and induces micronucleation in MCF-7 breast cancer cells

Holy, Jon

doi:10.1016/s1383-5718(02)00076-1

Cited by 98 publications

(78 citation statements)

References 54 publications

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“…5 It has been very recently shown that curcumin (diferuloylmethane), a natural dye from the rhizome of Curcuma longa and a known apoptotic inducer, downregulates survivin. 8 In other experiments, it has been shown that curcumin arrests MCF-7 cells in G 2 /M, disrupts mitotic spindle structure and induces micronucleation in MCF-7 breast cancer, 9 displaying cell morphology that fits very well to the mitotic catastrophe picture. Accordingly, we suppose that curcumin might disrupt mitotic spindle by decreasing survivin level and induce mitotic catastrophe, especially in cells with impaired DNA damage checkpoints and apoptotic signaling pathways.…”

mentioning

confidence: 81%

Resistance to apoptosis of HCW‐2 cells can be overcome by curcumin‐ or vincristine‐induced mitotic catastrophe

Magalska

Śliwińska

Szczepanowska

et al. 2006

Intl Journal of Cancer

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The term mitotic catastrophe has recently become widely used to describe a form of death affecting many cancer cells, which, because of severe DNA or mitotic spindle damage, are not able to bypass mitosis. We show here that cells of the HL-60-derived HCW-2 line highly resistant to apoptosis, upon treatment with curcumin or vincristine, undergo mitotic catastrophe that is finalized by caspase 3 activation and oligonucleosomal DNA degradation. Curcumin is a natural dye, derived from Curcuma longa that has been shown to induce cell death in many cancer cells. Both treatments decrease cell proliferation and cell survival, arrest cells in G 2 /M phase of cell cycle and induce morphological changes characterized by cell enlargement and micronucleation. ''Catastrophic'' cells comprise a separate subpopulation with less than 4 C DNA, as evidenced by flow and scanning cytometry. This subpopulation is MPM-2 positive. Thymidine block increased the number of cell arrested in the G 2 /M phase of cell cycle and curcumin effectiveness as an inducer of mitotic catastrophe. Curcumin, but not vincristine, acts on HCW-2 cells by inhibiting the expression of survivin, a modulator of cell division and apoptosis in cancer. Altogether our results show that apoptosis resistance can be overcome by inducing mitotic catastrophe in HCW-2 cells. ' 2006 Wiley-Liss, Inc.

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mentioning

confidence: 81%

Resistance to apoptosis of HCW‐2 cells can be overcome by curcumin‐ or vincristine‐induced mitotic catastrophe

Magalska

Śliwińska

Szczepanowska

et al. 2006

Intl Journal of Cancer

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“…The effects of Curcumin on cell cycle arrest are associated with structural changes of tubulin, followed by abnormal chromosome segregration [2,3]. To determine whether bDMC and DAC exert an effect on mitotic spindle organization, HCT116 cells treated for 24 hours with IC 50 doses were fixed and processed for immunofluorescence microscopy using anti-tubulin antibody and HOECHST to detect nuclear morphology.…”

Section: Treatment Of Hct116 Cells With Curcumin Derivatives Delays Mmentioning

confidence: 99%

“…Curcumin, a common flavoring agent in the spice turmeric, perturbs microtubule assembly dynamics through tubulin binding, which results in its conformational changes [2]. Significant depolymerization of interphase microtubules and mitotic spindle microtubules have been observed after Curcumin incubation of HeLa, MCF-7, HT-29 and HCT-15 cells, thus leading to a mitotic arrest [2][3][4].…”

Section: Introductionmentioning

confidence: 99%

Curcumin derivatives: Molecular basis of their anti-cancer activity

Basile

Ferrari

Lazzari

et al. 2009

Biochemical Pharmacology

160

125

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Curcumin, a phenolic compound from the plant Curcuma longa L., has shown a wide-spectrum of chemopreventive, anti-oxidant and anti-tumor properties. Although its promising chemotherapeutic activity, preclinical and clinical studies highlight Curcumin limited therapeutic application due to its instability in physiological conditions. To improve its stability and activity, many derivatives have been synthesized and studied, among which bis-DemethoxyCurcumin (bDMC) and diAcetylCurcumin (DAC). In this report, we show that both bDMC and DAC are more stable than Curcumin in physiological medium. To explore the mechanism of their chemotherapeutic effect, we studied their role in proliferation in the HCT116 human colon cancer cells. We correlated kinetic stability and cellular uptake data to their biological effects. Both bDMC and DAC impair correct spindles formation and induce a p53-and p21 CIP1/WAF1 -independent mitotic arrest, which is more stable and long-lasting for bDMC. A subsequent p53/p21 CIP1/WAF1 -dependent inhibition of G1 to S transition is triggered by Curcumin and DAC as a consequence of the mitotic slippage, preventing postmitotic cells from re-entering the cell cycle. Conversely, the G1/S arrest induced by bDMC is a direct effect of the drug and concomitant to the mitotic block. Finally, we demonstrate that bDMC induces rapid DNA double-strand breaks, moving for its possible development in anti-cancer clinical applications.

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“…The anti-carcinogenic properties of curcumin in animals have been demonstrated by its inhibition of tumor initiation induced by various carcinogens (21,22). This yellow pigment interrupts cell cycle, disrupts mitotic spindle structure, and induces micro-nucleation, thereby acting as anti-proliferative agent in various cancer cells (23). We have already reported that curcumin induces apoptosis in human breast carcinoma cells (20).…”

mentioning

confidence: 99%

Curcumin Selectively Induces Apoptosis in Deregulated Cyclin D1-expressed Cells at G2 Phase of Cell Cycle in a p53-dependent Manner

Choudhuri

Pal

Das

et al. 2005

Journal of Biological Chemistry

286

225

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Curcumin (diferuloylmethane) is known to induce apoptosis in tumor cells. In asynchronous cultures, with time-lapse video-micrography in combination with quantitative fluorescence microscopy, we have demonstrated that curcumin induces apoptosis at G 2 phase of cell cycle in deregulated cyclin D1-expressed mammary epithelial carcinoma cells, leaving its normal counterpart unaffected. In our search toward delineating the molecular mechanisms behind such differential activities of curcumin, we found that it selectively increases p53 expression at G 2 phase of carcinoma cells and releases cytochrome c from mitochondria, which is an essential requirement for apoptosis. Further experiments using p53-null as well as dominant-negative and wildtype p53-transfected cells have established that curcumin induces apoptosis in carcinoma cells via a p53-dependent pathway. On the other hand, curcumin reversibly inhibits normal mammary epithelial cell cycle progression by down-regulating cyclin D1 expression and blocking its association with Cdk4/Cdk6 as well as by inhibiting phosphorylation and inactivation of retinoblastoma protein. In addition, curcumin significantly up-regulates cell cycle inhibitory protein (p21Waf-1) in normal cells and arrests them in G 0 phase of cell cycle. Therefore, these cells escape from curcumin-induced apoptosis at G 2 phase. Interestingly, these processes remain unaffected by curcumin in carcinoma cells where cyclin D1 expression is high. Similarly, in ectopically overexpressed system, curcumin cannot down-regulate cyclin D1 and thus block cell cycle progression. Hence, these cells progress into G 2 phase and undergo apoptosis. These observations together suggest that curcumin may have a possible therapeutic potential in breast cancer patients.

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Curcumin disrupts mitotic spindle structure and induces micronucleation in MCF-7 breast cancer cells

Cited by 98 publications

References 54 publications

Resistance to apoptosis of HCW‐2 cells can be overcome by curcumin‐ or vincristine‐induced mitotic catastrophe

Resistance to apoptosis of HCW‐2 cells can be overcome by curcumin‐ or vincristine‐induced mitotic catastrophe

Curcumin derivatives: Molecular basis of their anti-cancer activity

Curcumin Selectively Induces Apoptosis in Deregulated Cyclin D1-expressed Cells at G2 Phase of Cell Cycle in a p53-dependent Manner

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