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

Gabor Halmos; Attila Nagy; Najib Lamharzi; Andrew V. Schally

doi:10.1016/S0304-3835(98)00316-4

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

Gabor Halmos, Attila Nagy, Najib Lamharzi, Andrew V. Schally

Research output: Contribution to journal › Article › peer-review

48 Scopus citations

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. Copyright (C) 1999.

Original language	English (US)
Pages (from-to)	129-136
Number of pages	8
Journal	Cancer letters
Volume	136
Issue number	2
DOIs	https://doi.org/10.1016/S0304-3835(98)00316-4
State	Published - Mar 1 1999
Externally published	Yes

Keywords

Breast cancer
LH-RH receptors
Targeted chemotherapeutic agents

ASJC Scopus subject areas

Cancer Research
Molecular Biology
Oncology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/S0304-3835(98)00316-4

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title = "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. Copyright (C) 1999.",

keywords = "Breast cancer, LH-RH receptors, Targeted chemotherapeutic agents",

author = "Gabor Halmos and Attila Nagy and Najib Lamharzi and Schally, {Andrew V.}",

note = "Funding Information: The authors wish to thank Dr. J.L. Wittliff (Hormone Receptor Laboratory, University of Louisville School of Medicine, Louisville, KY) for biopsy samples of human mammary cancers. We are grateful to Patricia Armatis and Agnes V. Kopp{\'a}n for their experimental assistance. The work described in this paper was supported by a grant from ASTA Medica to Tulane University School of Medicine and by the Medical Research Service of the Veterans Affairs Department (to A.V.S.).",

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AU - Nagy, Attila

AU - Lamharzi, Najib

AU - Schally, Andrew V.

N1 - Funding Information: The authors wish to thank Dr. J.L. Wittliff (Hormone Receptor Laboratory, University of Louisville School of Medicine, Louisville, KY) for biopsy samples of human mammary cancers. We are grateful to Patricia Armatis and Agnes V. Koppán for their experimental assistance. The work described in this paper was supported by a grant from ASTA Medica to Tulane University School of Medicine and by the Medical Research Service of the Veterans Affairs Department (to A.V.S.).

PY - 1999/3/1

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N2 - 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. Copyright (C) 1999.

AB - 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. Copyright (C) 1999.

KW - Breast cancer

KW - LH-RH receptors

KW - Targeted chemotherapeutic agents

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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