Cytotoxic analogs of luteinizing hormone-releasing hormone bind with high affinity to human breast cancers.
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.
Halmos
G
G
Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center, New Orleans, LA 70112-1262, USA.
Nagy
A
A
Lamharzi
N
N
Schally
A V
AV
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000378:metabolism*; D001667:Binding, Competitive; D001943:Breast Neoplasms / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000378:metabolism; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D011869:Radioligand Assay; D011966:Receptors, LHRH / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D012333:RNA, Messenger; D011966:Receptors, LHRH; C104648:AN 207; C080883:LHRH, lysine(6)-doxorubicin; D007987:Gonadotropin-Releasing Hormone; D004317:Doxorubicin