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  • Title: Cytotoxic analogs of luteinizing hormone-releasing hormone bind with high affinity to human breast cancers.
    Author: Halmos G, Nagy A, Lamharzi N, Schally AV.
    Journal: Cancer Lett; 1999 Mar 01; 136(2):129-36. PubMed ID: 10355741.
    Abstract:
    Recently, we developed two new cytotoxic analogs of luteinizing hormone-releasing hormone (LH-RH), AN-152 in which doxorubicin (DOX) is linked to [D-Lys6]LH-RH, and AN-207 which consists of 2-pyrrolino-DOX coupled to [D-Lys6]LH-RH. In this study, we examined binding of AN-152 and AN-207 to membranes of human breast cancer specimens and MCF-7 and MDA-MB-231 human breast cancer lines. Both cytotoxic analogs displayed IC50 values in the nanomolar concentration range (IC50 = 2-13 nM). Using radioligand binding studies, we characterized the receptors for LH-RH on membranes of breast cancers. In addition, the expression of mRNA for LH-RH receptors in MCF-7 and MDA-MB-231 cell lines was demonstrated by reverse transcription-polymerase chain reaction (RT-PCR). These highly active cytotoxic analogs of LH-RH have been designed as targeted chemotherapeutic agents for the treatment of various cancers expressing receptors for LH-RH.
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