Cytotoxic analogs of luteinizing hormone-releasing hormone bind with high affinity to human breast cancers.

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.

• Authors: G Halmos, A Nagy, N Lamharzi, A V Schally
• Journal: Cancer letters (Cancer Lett) Vol. 136 Issue 2 Pg. 129-36 (Mar 01 1999) ISSN: 0304-3835 [Print] Ireland
• PMID: 10355741 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antineoplastic Agents
• RNA, Messenger
• Receptors, LHRH
• AN 207
• LHRH, lysine(6)-doxorubicin
• Gonadotropin-Releasing Hormone
• Doxorubicin

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (metabolism)
• Binding, Competitive
• Breast Neoplasms (metabolism)
• Cell Membrane (metabolism)
• Doxorubicin (analogs & derivatives, metabolism)
• Female
• Gonadotropin-Releasing Hormone (analogs & derivatives, metabolism)
• Humans
• Middle Aged
• RNA, Messenger (metabolism)
• Radioligand Assay
• Receptors, LHRH (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Tumor Cells, Cultured