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Research ArticleExperimental Studies

Bis(4-hydroxy-2H-chromen-2-one) Coumarin Induces Apoptosis in MCF-7 Human Breast Cancer Cells Through Aromatase Inhibition

LAMIA HAMDAN RAMDANI, OUALID TALHI, CAROLINE DECOMBAT, MARION VERMERIE, ALEXANDRE BERRY, ARTUR SILVA, KHALDOUN BACHARI, MARIE-PAULE VASSON, LAETITIA DELORT and FLORENCE CALDEFIE-CHÉZET
Anticancer Research November 2019, 39 (11) 6107-6114; DOI: https://doi.org/10.21873/anticanres.13818
LAMIA HAMDAN RAMDANI
1Scientific and Technical Research Center in Physico-Chemical Analysis (CRAPC), Tipaza, Algeria
2Clermont Auvergne University, INRA, UNH, Human Nutrition unit, CRNH Auvergne, Clermont Ferrand, France
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  • For correspondence: lamia_pharm{at}yahoo.fr
OUALID TALHI
1Scientific and Technical Research Center in Physico-Chemical Analysis (CRAPC), Tipaza, Algeria
3Organic Chemistry, Natural Products and Agrifood (QOPNA), Department of Chemistry & QOPNA, University of Aveiro, Aveiro, Portugal
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CAROLINE DECOMBAT
2Clermont Auvergne University, INRA, UNH, Human Nutrition unit, CRNH Auvergne, Clermont Ferrand, France
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MARION VERMERIE
2Clermont Auvergne University, INRA, UNH, Human Nutrition unit, CRNH Auvergne, Clermont Ferrand, France
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ALEXANDRE BERRY
2Clermont Auvergne University, INRA, UNH, Human Nutrition unit, CRNH Auvergne, Clermont Ferrand, France
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ARTUR SILVA
3Organic Chemistry, Natural Products and Agrifood (QOPNA), Department of Chemistry & QOPNA, University of Aveiro, Aveiro, Portugal
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KHALDOUN BACHARI
1Scientific and Technical Research Center in Physico-Chemical Analysis (CRAPC), Tipaza, Algeria
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MARIE-PAULE VASSON
2Clermont Auvergne University, INRA, UNH, Human Nutrition unit, CRNH Auvergne, Clermont Ferrand, France
4Anticancer Center Jean-Perrin, Clermont Ferrand, France
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LAETITIA DELORT
2Clermont Auvergne University, INRA, UNH, Human Nutrition unit, CRNH Auvergne, Clermont Ferrand, France
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FLORENCE CALDEFIE-CHÉZET
2Clermont Auvergne University, INRA, UNH, Human Nutrition unit, CRNH Auvergne, Clermont Ferrand, France
5CLARA, Lyon Auvergne Rhone Alpes canceropole, Lyon, France
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    Figure 1.

    Synthesis of bis(4-hydroxy-2H-chromen-2-one) coumarin (4HC).

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    Figure 2.

    Proliferation of MCF-10a mammary non-cancerous cells (A) and MCF-7 mammary cancer cells (B) treated with 4HC. 4HC showed significant anti-proliferative activities in MCF-7 cells in time and concentration-dependent manner. *p≤0.05; **p≤0.01; ***p≤0.001 compared to the control value. Experiments were repeated in triplicate. Ctl, Control; Doxo, doxorubicin.

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    Figure 3.

    MCF-7 cell cycle distribution analysis (A). The percentage of cells in the G1, S, and G2/M phases of the cell cycle are shown, following a treatment with 25 and 50 μM of 4HC for 72 h (B). *p≤0.05; **p≤0.01 compared to the control group. Experiments were repeated in triplicate. PI, Propidium iodide; ctl, control.

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    Figure 4.

    Evaluation of apoptosis in MCF-7 cells treated with 4HC. Images (captured by FCS express 6 image Cytometry, De Novo software) showed apoptosis in MCF-7 cells. Control and 4HC-treated cells for 72 h were stained with Annexin V-FITC and PI. (FITC-/PI-) reflected living cells, fluorescence (FITC+/PI-) represented early apoptotic cells, and fluorescence (FITC+/PI+) showed late apoptotic cells (A). The percentage of apoptosis is represented as the mean±SD (B). *p≤0.05; **p≤0.01, compared to the control. Experiments were repeated in triplicate. Ctl, Control.

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    Figure 5.

    The relative expression of the pro-apoptotic Bax, and caspase 3 genes, the anti-apoptotic gene Bcl-2 and the aromatase gene CYP19A1 levels in 4HC-treated and control MCF-7 cells (for 72 h) were analyzed using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). *p≤0.05; **p≤0.01, compared to the control group. Experiments were repeated in triplicate. Ctl, Control.

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November 2019
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Bis(4-hydroxy-2H-chromen-2-one) Coumarin Induces Apoptosis in MCF-7 Human Breast Cancer Cells Through Aromatase Inhibition
LAMIA HAMDAN RAMDANI, OUALID TALHI, CAROLINE DECOMBAT, MARION VERMERIE, ALEXANDRE BERRY, ARTUR SILVA, KHALDOUN BACHARI, MARIE-PAULE VASSON, LAETITIA DELORT, FLORENCE CALDEFIE-CHÉZET
Anticancer Research Nov 2019, 39 (11) 6107-6114; DOI: 10.21873/anticanres.13818

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Bis(4-hydroxy-2H-chromen-2-one) Coumarin Induces Apoptosis in MCF-7 Human Breast Cancer Cells Through Aromatase Inhibition
LAMIA HAMDAN RAMDANI, OUALID TALHI, CAROLINE DECOMBAT, MARION VERMERIE, ALEXANDRE BERRY, ARTUR SILVA, KHALDOUN BACHARI, MARIE-PAULE VASSON, LAETITIA DELORT, FLORENCE CALDEFIE-CHÉZET
Anticancer Research Nov 2019, 39 (11) 6107-6114; DOI: 10.21873/anticanres.13818
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Keywords

  • Coumarin derivative
  • Bis(4-hydroxy-2H-chromen-2-one)
  • Breast cancer
  • cell proliferation
  • cell cycle
  • apoptosis
  • aromatase inhibition
  • MCF-7 breast cancer cells
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