Bombesin and epidermal growth factor potentiate the effect of cytotoxic LH-RH analog AN-152 in vitro.

Linda J. Krebs, Xiaopeng Wang, Atilla Nagy, Andrew V Schally, Paras N. Prasad, Charles Liebow

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The conjugation of doxorubicin with [D-Lys6] Luteinizing Hormone-Releasing Hormone (LH-RH), yields AN-152, a cytotoxic analog that can be targeted to tumor cells expressing LH-RH receptors. This conjugate is more potent against LH-RH receptor positive cancer cells and has less peripheral toxicity than free doxorubicin. The proliferation of MCF-7 human breast cancer cells in vitro is inhibited by AN-152 and this effect can be augmented by the up-regulation of LH-RH receptor expression through stimulation of tyrosine phosphorylation with epidermal growth factor (EGF). Bombesin and gastrin releasing peptide increase tyrosine phosphorylation and can act synergistically with EGF, as well as independently. The aim of this study was to demonstrate that bombesin enhances cytotoxic sensitivity of MCF-7 cells to AN-152 and that a significantly higher efficacy of the drug can be achieved in cells exposed to both bombesin and EGF. The cells were pretreated with bombesin and/or EGF, and then exposed to 0-10 micro M AN-152 for 96 h for determination of cytotoxicity. In addition, cells pretreated with bombesin and/or EGF were exposed for 1 h to 0.6 micro M AN-152 labeled with a two-photon fluorophore (AN-152:C625) for fluorescent imaging of drug entry. Bombesin as well as EGF increased the uptake and cytotoxicity of AN-152 in MCF-7 cells. The exposure of the cells to both EGF and bombesin produces a synergistic effect and results in increased cellular entry and cytotoxicity of AN-152. These results suggest that the activation of LH-RH receptors by compounds that increase tyrosine phosphorylation could further improve the response to targeted chemotherapy with AN-152.

Original languageEnglish
Pages (from-to)1325-1329
Number of pages5
JournalInternational Journal of Oncology
Volume21
Issue number6
StatePublished - Dec 1 2002
Externally publishedYes

Fingerprint

Bombesin
Epidermal Growth Factor
Gonadotropin-Releasing Hormone
LHRH Receptors
Tyrosine
MCF-7 Cells
Phosphorylation
Doxorubicin
Gastrin-Releasing Peptide
lysine(6)-doxorubicin LHRH
In Vitro Techniques
Photons
Pharmaceutical Preparations
Neoplasms
Up-Regulation
Breast Neoplasms
Drug Therapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Bombesin and epidermal growth factor potentiate the effect of cytotoxic LH-RH analog AN-152 in vitro. / Krebs, Linda J.; Wang, Xiaopeng; Nagy, Atilla; Schally, Andrew V; Prasad, Paras N.; Liebow, Charles.

In: International Journal of Oncology, Vol. 21, No. 6, 01.12.2002, p. 1325-1329.

Research output: Contribution to journalArticle

Krebs, Linda J. ; Wang, Xiaopeng ; Nagy, Atilla ; Schally, Andrew V ; Prasad, Paras N. ; Liebow, Charles. / Bombesin and epidermal growth factor potentiate the effect of cytotoxic LH-RH analog AN-152 in vitro. In: International Journal of Oncology. 2002 ; Vol. 21, No. 6. pp. 1325-1329.
@article{e537338473e74f87ad02583703fd0a7a,
title = "Bombesin and epidermal growth factor potentiate the effect of cytotoxic LH-RH analog AN-152 in vitro.",
abstract = "The conjugation of doxorubicin with [D-Lys6] Luteinizing Hormone-Releasing Hormone (LH-RH), yields AN-152, a cytotoxic analog that can be targeted to tumor cells expressing LH-RH receptors. This conjugate is more potent against LH-RH receptor positive cancer cells and has less peripheral toxicity than free doxorubicin. The proliferation of MCF-7 human breast cancer cells in vitro is inhibited by AN-152 and this effect can be augmented by the up-regulation of LH-RH receptor expression through stimulation of tyrosine phosphorylation with epidermal growth factor (EGF). Bombesin and gastrin releasing peptide increase tyrosine phosphorylation and can act synergistically with EGF, as well as independently. The aim of this study was to demonstrate that bombesin enhances cytotoxic sensitivity of MCF-7 cells to AN-152 and that a significantly higher efficacy of the drug can be achieved in cells exposed to both bombesin and EGF. The cells were pretreated with bombesin and/or EGF, and then exposed to 0-10 micro M AN-152 for 96 h for determination of cytotoxicity. In addition, cells pretreated with bombesin and/or EGF were exposed for 1 h to 0.6 micro M AN-152 labeled with a two-photon fluorophore (AN-152:C625) for fluorescent imaging of drug entry. Bombesin as well as EGF increased the uptake and cytotoxicity of AN-152 in MCF-7 cells. The exposure of the cells to both EGF and bombesin produces a synergistic effect and results in increased cellular entry and cytotoxicity of AN-152. These results suggest that the activation of LH-RH receptors by compounds that increase tyrosine phosphorylation could further improve the response to targeted chemotherapy with AN-152.",
author = "Krebs, {Linda J.} and Xiaopeng Wang and Atilla Nagy and Schally, {Andrew V} and Prasad, {Paras N.} and Charles Liebow",
year = "2002",
month = "12",
day = "1",
language = "English",
volume = "21",
pages = "1325--1329",
journal = "International Journal of Oncology",
issn = "1019-6439",
publisher = "Spandidos Publications",
number = "6",

}

TY - JOUR

T1 - Bombesin and epidermal growth factor potentiate the effect of cytotoxic LH-RH analog AN-152 in vitro.

AU - Krebs, Linda J.

AU - Wang, Xiaopeng

AU - Nagy, Atilla

AU - Schally, Andrew V

AU - Prasad, Paras N.

AU - Liebow, Charles

PY - 2002/12/1

Y1 - 2002/12/1

N2 - The conjugation of doxorubicin with [D-Lys6] Luteinizing Hormone-Releasing Hormone (LH-RH), yields AN-152, a cytotoxic analog that can be targeted to tumor cells expressing LH-RH receptors. This conjugate is more potent against LH-RH receptor positive cancer cells and has less peripheral toxicity than free doxorubicin. The proliferation of MCF-7 human breast cancer cells in vitro is inhibited by AN-152 and this effect can be augmented by the up-regulation of LH-RH receptor expression through stimulation of tyrosine phosphorylation with epidermal growth factor (EGF). Bombesin and gastrin releasing peptide increase tyrosine phosphorylation and can act synergistically with EGF, as well as independently. The aim of this study was to demonstrate that bombesin enhances cytotoxic sensitivity of MCF-7 cells to AN-152 and that a significantly higher efficacy of the drug can be achieved in cells exposed to both bombesin and EGF. The cells were pretreated with bombesin and/or EGF, and then exposed to 0-10 micro M AN-152 for 96 h for determination of cytotoxicity. In addition, cells pretreated with bombesin and/or EGF were exposed for 1 h to 0.6 micro M AN-152 labeled with a two-photon fluorophore (AN-152:C625) for fluorescent imaging of drug entry. Bombesin as well as EGF increased the uptake and cytotoxicity of AN-152 in MCF-7 cells. The exposure of the cells to both EGF and bombesin produces a synergistic effect and results in increased cellular entry and cytotoxicity of AN-152. These results suggest that the activation of LH-RH receptors by compounds that increase tyrosine phosphorylation could further improve the response to targeted chemotherapy with AN-152.

AB - The conjugation of doxorubicin with [D-Lys6] Luteinizing Hormone-Releasing Hormone (LH-RH), yields AN-152, a cytotoxic analog that can be targeted to tumor cells expressing LH-RH receptors. This conjugate is more potent against LH-RH receptor positive cancer cells and has less peripheral toxicity than free doxorubicin. The proliferation of MCF-7 human breast cancer cells in vitro is inhibited by AN-152 and this effect can be augmented by the up-regulation of LH-RH receptor expression through stimulation of tyrosine phosphorylation with epidermal growth factor (EGF). Bombesin and gastrin releasing peptide increase tyrosine phosphorylation and can act synergistically with EGF, as well as independently. The aim of this study was to demonstrate that bombesin enhances cytotoxic sensitivity of MCF-7 cells to AN-152 and that a significantly higher efficacy of the drug can be achieved in cells exposed to both bombesin and EGF. The cells were pretreated with bombesin and/or EGF, and then exposed to 0-10 micro M AN-152 for 96 h for determination of cytotoxicity. In addition, cells pretreated with bombesin and/or EGF were exposed for 1 h to 0.6 micro M AN-152 labeled with a two-photon fluorophore (AN-152:C625) for fluorescent imaging of drug entry. Bombesin as well as EGF increased the uptake and cytotoxicity of AN-152 in MCF-7 cells. The exposure of the cells to both EGF and bombesin produces a synergistic effect and results in increased cellular entry and cytotoxicity of AN-152. These results suggest that the activation of LH-RH receptors by compounds that increase tyrosine phosphorylation could further improve the response to targeted chemotherapy with AN-152.

UR - http://www.scopus.com/inward/record.url?scp=1842845182&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1842845182&partnerID=8YFLogxK

M3 - Article

C2 - 12429984

AN - SCOPUS:1842845182

VL - 21

SP - 1325

EP - 1329

JO - International Journal of Oncology

JF - International Journal of Oncology

SN - 1019-6439

IS - 6

ER -