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Genistein modulates the anti-tumor activity of cisplatin in MCF-7 breast and HT-29 colon cancer cells

  • Molecular Toxicology
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Abstract

The function of genistein (GEN) on tumor prevention and tumor promotion is discussed controversially. A possible interference of GEN with chemotherapy has been only rarely addressed so far. In this study, effects of GEN on the anti-tumor activity of cisplatin (CIS) were investigated in the presence and absence of estradiol (10−10 M) in MCF-7 breast and HT-29 colon cancer cells. Cells were treated with graded concentrations of GEN (10−4–10−6 M), E2, CIS and combinations. Cell growth, proliferation and apoptosis were determined as well as the expression level of PCNA, Ki67 and BCL-2 family members. CIS and GEN 10−4 M inhibited cell growth and induced apoptosis in MCF-7 and HT-29 cells in the presence and absence of E2. Co-treatment with CIS and 10−4M GEN resulted in additive effects. In concentrations of 10−5 and 10−6 M, GEN stimulated cell growth in MCF-7 cells. It promoted proliferation, inhibited apoptosis and counteracted the anti-tumor activity of CIS in MCF-7 and HT-29 cells. Particularly the ability of CIS to induce apoptosis was antagonized. In ER alpha-positive MCF-7 cells, but not in ER alpha-negative HT-29 cells, E2 was able to neutralize the anti-CIS effects of GEN. Our data provide evidence that GEN in the absence of E2, a situation which occurs in postmenopausal women, directly affects the anti-tumor activity of cytostatic drugs like CIS. The exact molecular mechanism has to be investigated in future studies.

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Abbreviations

CIS:

Cisplatin

GEN:

Genistein

ER:

Estrogen receptor

E2 :

Estradiol

PMSF:

Phenylmethanesulfonylfluoride

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Acknowledgments

We appreciate DAAD scholarship’s financial support. We thank Raoul Kempkes for his help on the flow cytometry assay and Prof. Pablo Steinberg for supporting with HCEC cells. We also thank Carmen Weigt for reading the manuscript. This study was supported by a grant support from Sino-German Center (No. GZ731) and by International Science and Technology Cooperation Projects (No. 2010DFA31780).

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Authors and Affiliations

  1. Department of Cellular and Molecular Sports Medicine, Institute of Cardiovascular Research and Sports Medicine, German Sports University Cologne, Am Sportpark Muengersdorf 6, 50933, Koeln, Germany

    Xiao-Juan Hu, Felix M. Kluxen & Patrick Diel

  2. State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, 330047, China

    Xiao-Juan Hu & Ming-Yong Xie

  3. Basic Medical College, Nanchang University, Nanchang, 330006, China

    Xiao-Juan Hu

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  1. Xiao-Juan Hu
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  2. Ming-Yong Xie
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Correspondence to Ming-Yong Xie or Patrick Diel.

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Hu, XJ., Xie, MY., Kluxen, F.M. et al. Genistein modulates the anti-tumor activity of cisplatin in MCF-7 breast and HT-29 colon cancer cells. Arch Toxicol 88, 625–635 (2014). https://doi.org/10.1007/s00204-013-1184-4

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  • DOI: https://doi.org/10.1007/s00204-013-1184-4

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