Inhibition of human experimental prostate cancers by a targeted cytotoxic luteinizing hormone-releasing hormone analog AN-207

Anton Stangelberger, Andrew V Schally, Attila Nagy, Karoly Szepeshazi, Celia A. Kanashiro, Gabor Halmos

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

BACKGROUND. Receptors for luteinizing hormone-releasing hormone (LHRH) on human prostate cancers can be used for targeted chemotherapy with cytotoxic analogs of LHRH, such as AN-207, which consists of superactive doxorubicin derivative 2-pyrrolino doxorubicin (AN-201) linked to carrier [D-Lys 6] LHRH. METHODS. The effects of AN-207 and AN-201 were investigated in DU-145 androgen independent and LuCaP-35 androgen sensitive human prostate cancers xenografted into nude mice. Toxicity was evaluated by survival rates, changes in body weights, and leukocyte counts. LHRH receptors on DU-145 and LuCaP-35 tumors were evaluated by radioreceptor assays and RT-PCR. The effects on apoptosis and cell proliferation were investigated by histology and evaluation of apoptotic oncogenes Bcl-2 and Bax by Western Blot analysis. RESULTS. AN-207 inhibited growth of DU-145 tumors significantly by 75% (P < 0.01) and LuCaP-35 human prostate cancers by 80% (P < 0.01), and was less toxic than AN-201. Receptors for LHRH were expressed on DU-145 and LuCaP-35 tumors. Blockade of LHRH receptors with LHRH agonist Triptorelin nullified the effects of AN-207. Treatment with AN-207, but not with AN-201, decreased Bcl-2/Bax ratio in DU-145 tumors and Bcl-2 in LuCaP-35 tumors indicating an increase in apoptotic activity. AN-207, but not AN-201, decreased cell proliferation in both models. CONCLUSIONS. Targeted chemotherapy with AN-207 could be considered for treatment of advanced prostate cancer.

Original languageEnglish
Pages (from-to)200-210
Number of pages11
JournalProstate
Volume66
Issue number2
DOIs
StatePublished - Feb 1 2006
Externally publishedYes

Fingerprint

Gonadotropin-Releasing Hormone
Prostatic Neoplasms
LHRH Receptors
Neoplasms
Doxorubicin
Androgens
Triptorelin Pamoate
Cell Proliferation
Drug Therapy
Radioligand Assay
Body Weight Changes
Poisons
AN 207
Leukocyte Count
Oncogenes
Nude Mice
Histology
Western Blotting
AN 204
Apoptosis

Keywords

  • Cytotoxic LH-RH analog
  • LH-RH receptor
  • Prostate cancer
  • Targeted therapy

ASJC Scopus subject areas

  • Urology

Cite this

Inhibition of human experimental prostate cancers by a targeted cytotoxic luteinizing hormone-releasing hormone analog AN-207. / Stangelberger, Anton; Schally, Andrew V; Nagy, Attila; Szepeshazi, Karoly; Kanashiro, Celia A.; Halmos, Gabor.

In: Prostate, Vol. 66, No. 2, 01.02.2006, p. 200-210.

Research output: Contribution to journalArticle

Stangelberger, Anton ; Schally, Andrew V ; Nagy, Attila ; Szepeshazi, Karoly ; Kanashiro, Celia A. ; Halmos, Gabor. / Inhibition of human experimental prostate cancers by a targeted cytotoxic luteinizing hormone-releasing hormone analog AN-207. In: Prostate. 2006 ; Vol. 66, No. 2. pp. 200-210.
@article{177358279da24d588497a7a1e5dc8326,
title = "Inhibition of human experimental prostate cancers by a targeted cytotoxic luteinizing hormone-releasing hormone analog AN-207",
abstract = "BACKGROUND. Receptors for luteinizing hormone-releasing hormone (LHRH) on human prostate cancers can be used for targeted chemotherapy with cytotoxic analogs of LHRH, such as AN-207, which consists of superactive doxorubicin derivative 2-pyrrolino doxorubicin (AN-201) linked to carrier [D-Lys 6] LHRH. METHODS. The effects of AN-207 and AN-201 were investigated in DU-145 androgen independent and LuCaP-35 androgen sensitive human prostate cancers xenografted into nude mice. Toxicity was evaluated by survival rates, changes in body weights, and leukocyte counts. LHRH receptors on DU-145 and LuCaP-35 tumors were evaluated by radioreceptor assays and RT-PCR. The effects on apoptosis and cell proliferation were investigated by histology and evaluation of apoptotic oncogenes Bcl-2 and Bax by Western Blot analysis. RESULTS. AN-207 inhibited growth of DU-145 tumors significantly by 75{\%} (P < 0.01) and LuCaP-35 human prostate cancers by 80{\%} (P < 0.01), and was less toxic than AN-201. Receptors for LHRH were expressed on DU-145 and LuCaP-35 tumors. Blockade of LHRH receptors with LHRH agonist Triptorelin nullified the effects of AN-207. Treatment with AN-207, but not with AN-201, decreased Bcl-2/Bax ratio in DU-145 tumors and Bcl-2 in LuCaP-35 tumors indicating an increase in apoptotic activity. AN-207, but not AN-201, decreased cell proliferation in both models. CONCLUSIONS. Targeted chemotherapy with AN-207 could be considered for treatment of advanced prostate cancer.",
keywords = "Cytotoxic LH-RH analog, LH-RH receptor, Prostate cancer, Targeted therapy",
author = "Anton Stangelberger and Schally, {Andrew V} and Attila Nagy and Karoly Szepeshazi and Kanashiro, {Celia A.} and Gabor Halmos",
year = "2006",
month = "2",
day = "1",
doi = "10.1002/pros.20335",
language = "English",
volume = "66",
pages = "200--210",
journal = "Prostate",
issn = "0270-4137",
publisher = "Wiley-Liss Inc.",
number = "2",

}

TY - JOUR

T1 - Inhibition of human experimental prostate cancers by a targeted cytotoxic luteinizing hormone-releasing hormone analog AN-207

AU - Stangelberger, Anton

AU - Schally, Andrew V

AU - Nagy, Attila

AU - Szepeshazi, Karoly

AU - Kanashiro, Celia A.

AU - Halmos, Gabor

PY - 2006/2/1

Y1 - 2006/2/1

N2 - BACKGROUND. Receptors for luteinizing hormone-releasing hormone (LHRH) on human prostate cancers can be used for targeted chemotherapy with cytotoxic analogs of LHRH, such as AN-207, which consists of superactive doxorubicin derivative 2-pyrrolino doxorubicin (AN-201) linked to carrier [D-Lys 6] LHRH. METHODS. The effects of AN-207 and AN-201 were investigated in DU-145 androgen independent and LuCaP-35 androgen sensitive human prostate cancers xenografted into nude mice. Toxicity was evaluated by survival rates, changes in body weights, and leukocyte counts. LHRH receptors on DU-145 and LuCaP-35 tumors were evaluated by radioreceptor assays and RT-PCR. The effects on apoptosis and cell proliferation were investigated by histology and evaluation of apoptotic oncogenes Bcl-2 and Bax by Western Blot analysis. RESULTS. AN-207 inhibited growth of DU-145 tumors significantly by 75% (P < 0.01) and LuCaP-35 human prostate cancers by 80% (P < 0.01), and was less toxic than AN-201. Receptors for LHRH were expressed on DU-145 and LuCaP-35 tumors. Blockade of LHRH receptors with LHRH agonist Triptorelin nullified the effects of AN-207. Treatment with AN-207, but not with AN-201, decreased Bcl-2/Bax ratio in DU-145 tumors and Bcl-2 in LuCaP-35 tumors indicating an increase in apoptotic activity. AN-207, but not AN-201, decreased cell proliferation in both models. CONCLUSIONS. Targeted chemotherapy with AN-207 could be considered for treatment of advanced prostate cancer.

AB - BACKGROUND. Receptors for luteinizing hormone-releasing hormone (LHRH) on human prostate cancers can be used for targeted chemotherapy with cytotoxic analogs of LHRH, such as AN-207, which consists of superactive doxorubicin derivative 2-pyrrolino doxorubicin (AN-201) linked to carrier [D-Lys 6] LHRH. METHODS. The effects of AN-207 and AN-201 were investigated in DU-145 androgen independent and LuCaP-35 androgen sensitive human prostate cancers xenografted into nude mice. Toxicity was evaluated by survival rates, changes in body weights, and leukocyte counts. LHRH receptors on DU-145 and LuCaP-35 tumors were evaluated by radioreceptor assays and RT-PCR. The effects on apoptosis and cell proliferation were investigated by histology and evaluation of apoptotic oncogenes Bcl-2 and Bax by Western Blot analysis. RESULTS. AN-207 inhibited growth of DU-145 tumors significantly by 75% (P < 0.01) and LuCaP-35 human prostate cancers by 80% (P < 0.01), and was less toxic than AN-201. Receptors for LHRH were expressed on DU-145 and LuCaP-35 tumors. Blockade of LHRH receptors with LHRH agonist Triptorelin nullified the effects of AN-207. Treatment with AN-207, but not with AN-201, decreased Bcl-2/Bax ratio in DU-145 tumors and Bcl-2 in LuCaP-35 tumors indicating an increase in apoptotic activity. AN-207, but not AN-201, decreased cell proliferation in both models. CONCLUSIONS. Targeted chemotherapy with AN-207 could be considered for treatment of advanced prostate cancer.

KW - Cytotoxic LH-RH analog

KW - LH-RH receptor

KW - Prostate cancer

KW - Targeted therapy

UR - http://www.scopus.com/inward/record.url?scp=31944437524&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=31944437524&partnerID=8YFLogxK

U2 - 10.1002/pros.20335

DO - 10.1002/pros.20335

M3 - Article

VL - 66

SP - 200

EP - 210

JO - Prostate

JF - Prostate

SN - 0270-4137

IS - 2

ER -