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A Novel Approach of Targeted Ablation of Mammary Carcinoma Cells Through Luteinizing Hormone Receptors using Hecate-CGβ Conjugate

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Abstract

Recent studies have shown that human and animal mammary gland carcinoma cell line express luteinizing hormone receptors (LHRs). We have examined the cytotoxic effect of Hecate-CGβ conjugate, that is, fusion of a lytic peptide (Hecate) and a 15-amino acid fragment of the CGβ-chain in vitro. To test the hypothesis that the Hecate-CGβ conjugate selectively abolishes cells possessing LHR, estrogen dependent and independent human breast cancer cell lines (MCF-7; MDA-MB-231) and a mouse Leydig tumor cell line (BLT-1) were treated in vitro with Hecate-CGβ conjugate and Hecate alone. Cytotoxic effects of the Hecate-CGβ conjugate and the Hecate alone was measured by lactate dehydrogenase (LDH) release immediately after treatment. We observed that the Hecate-CGβ conjugate selectively, in dose-dependent manner destroys cells possessing LHR in lower concentrations of preparate comparing to the Hecate alone and that the cytotoxic effect is strongly correlated with the number of LHR. Using Western blot analysis we characterized the LHR on membranes of MDA-MB-231, MCF-7 and BLT-1 tumor cell lines. In addition, we showed the evaluation of inhibition potential of the Hecate-CGβ conjugate to LHR. At a concentration of 33 µM the conjugate inhibited (50%; IC50) the binding of CG to LHR.

We suggest further development of this novel approach for the treatment of breast cancer by the Hecate-CGβ for in vivo trials.

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Authors and Affiliations

  1. Institute of Animal Reproduction and Food Research Polish Academy of Sciences, Olsztyn, Poland

    Gabriel Bodek, Monika Zaleska & Adam J. Ziecik

  2. Department of Physiology, University of Turku, Finland

    Nafis Ahmed Rahman & Ilpo Huhtaniemi

  3. Peptide and Protein Laboratory, Haartman Institute, University of Helsinki, Finland

    Rabah Soliymani & Hikka Lankinen

  4. Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, USA

    William Hansel

Authors
  1. Gabriel Bodek
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  2. Nafis Ahmed Rahman
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  3. Monika Zaleska
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  4. Rabah Soliymani
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  5. Hikka Lankinen
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  6. William Hansel
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  7. Ilpo Huhtaniemi
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  8. Adam J. Ziecik
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Bodek, G., Ahmed Rahman, N., Zaleska, M. et al. A Novel Approach of Targeted Ablation of Mammary Carcinoma Cells Through Luteinizing Hormone Receptors using Hecate-CGβ Conjugate. Breast Cancer Res Treat 79, 1–10 (2003). https://doi.org/10.1023/A:1023351819956

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