Targeted cytotoxic analog of luteinizing hormone-releasing hormone AN- 207 inhibits the growth of PC-82 human prostate cancer in nude mice

M. Koppán, Attila Nagy, Andrew V. Schally, Artur Plonowski, Gábor Halmos, José M. Arencibia, Kate Groot

Research output: Contribution to journalArticle

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Abstract

BACKGROUND. Receptors for luteinizing hormone-releasing hormone (LH-RH) found in prostate cancers might be used for targeting of chemotherapeutic agents. Doxorubicin derivative 2-pyrrolinodoxorubicin (AN-201) can be linked to carrier analog [D-Lys6]LH-RH to form the targeted cytotoxic analog of LH- RH, AN-207. METHODS. We evaluated the effects of AN-207 and its components on the growth of LH-RH receptor-positive human prostate cancer PC-82 xenografted into nude mice. Analog AN-207, radical AN-201, carrier [D-Lys6]LH-RH, or a mixture of [D-Lys6]LH-RH and AN-201 were injected intravenously once at doses of 200 nmol/kg. Tumor growth, body weight, total WBC counts, and serum prostate-specific antigen (PSA) were determined. Receptors for LH-RH on PC- 82 tumors were evaluated, and the expression of mRNA for LH-RH receptors was assessed by RT-PCR. RESULTS. Eight weeks after administration of cytotoxic analog AN-207, there was a 67.8% reduction in tumor volume (P <0.01), 70.7% decrease in tumor burden (P <0.01), and 36.5% decrease in serum PSA levels (P <0.01) as compared with controls. Only one of 8 animals treated with AN- 207 died. Cytotoxic radical AN-201 caused a 34.2% (not significant, NS) reduction in tumor volume with no change in serum PSA, and killed 3 of 8 mice due to toxicity. Carrier [D-Lys6]LH-RH and the unconjugated mixture of [D- Lys6]LH-RH and AN-201 had no effect on tumor growth. LH-RH receptors as well as the expression of their mRNA were found in PC-82 tumors. CONCLUSIONS. The cytotoxic analog of LH-RH AN-207 powerfully inhibited growth of PC-82 human prostate cancer with only minor toxicity. Targeted cytotoxic LH-RH analogs may be useful for treatment of prostate cancer.

Original languageEnglish
Pages (from-to)151-158
Number of pages8
JournalProstate
Volume38
Issue number2
DOIs
Publication statusPublished - 1999

Fingerprint

Nude Mice
Gonadotropin-Releasing Hormone
LHRH Receptors
Prostatic Neoplasms
Growth
Prostate-Specific Antigen
Tumor Burden
Neoplasms
Serum
Messenger RNA
AN 207
Doxorubicin
AN 204
Body Weight
Polymerase Chain Reaction

Keywords

  • 2- pyrrolinodoxorubicin
  • LH-RH receptor
  • PC-82 tumor
  • Prostate cancer
  • Targeted chemotherapy

ASJC Scopus subject areas

  • Urology

Cite this

Targeted cytotoxic analog of luteinizing hormone-releasing hormone AN- 207 inhibits the growth of PC-82 human prostate cancer in nude mice. / Koppán, M.; Nagy, Attila; Schally, Andrew V.; Plonowski, Artur; Halmos, Gábor; Arencibia, José M.; Groot, Kate.

In: Prostate, Vol. 38, No. 2, 1999, p. 151-158.

Research output: Contribution to journalArticle

Koppán, M. ; Nagy, Attila ; Schally, Andrew V. ; Plonowski, Artur ; Halmos, Gábor ; Arencibia, José M. ; Groot, Kate. / Targeted cytotoxic analog of luteinizing hormone-releasing hormone AN- 207 inhibits the growth of PC-82 human prostate cancer in nude mice. In: Prostate. 1999 ; Vol. 38, No. 2. pp. 151-158.
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abstract = "BACKGROUND. Receptors for luteinizing hormone-releasing hormone (LH-RH) found in prostate cancers might be used for targeting of chemotherapeutic agents. Doxorubicin derivative 2-pyrrolinodoxorubicin (AN-201) can be linked to carrier analog [D-Lys6]LH-RH to form the targeted cytotoxic analog of LH- RH, AN-207. METHODS. We evaluated the effects of AN-207 and its components on the growth of LH-RH receptor-positive human prostate cancer PC-82 xenografted into nude mice. Analog AN-207, radical AN-201, carrier [D-Lys6]LH-RH, or a mixture of [D-Lys6]LH-RH and AN-201 were injected intravenously once at doses of 200 nmol/kg. Tumor growth, body weight, total WBC counts, and serum prostate-specific antigen (PSA) were determined. Receptors for LH-RH on PC- 82 tumors were evaluated, and the expression of mRNA for LH-RH receptors was assessed by RT-PCR. RESULTS. Eight weeks after administration of cytotoxic analog AN-207, there was a 67.8{\%} reduction in tumor volume (P <0.01), 70.7{\%} decrease in tumor burden (P <0.01), and 36.5{\%} decrease in serum PSA levels (P <0.01) as compared with controls. Only one of 8 animals treated with AN- 207 died. Cytotoxic radical AN-201 caused a 34.2{\%} (not significant, NS) reduction in tumor volume with no change in serum PSA, and killed 3 of 8 mice due to toxicity. Carrier [D-Lys6]LH-RH and the unconjugated mixture of [D- Lys6]LH-RH and AN-201 had no effect on tumor growth. LH-RH receptors as well as the expression of their mRNA were found in PC-82 tumors. CONCLUSIONS. The cytotoxic analog of LH-RH AN-207 powerfully inhibited growth of PC-82 human prostate cancer with only minor toxicity. Targeted cytotoxic LH-RH analogs may be useful for treatment of prostate cancer.",
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T1 - Targeted cytotoxic analog of luteinizing hormone-releasing hormone AN- 207 inhibits the growth of PC-82 human prostate cancer in nude mice

AU - Koppán, M.

AU - Nagy, Attila

AU - Schally, Andrew V.

AU - Plonowski, Artur

AU - Halmos, Gábor

AU - Arencibia, José M.

AU - Groot, Kate

PY - 1999

Y1 - 1999

N2 - BACKGROUND. Receptors for luteinizing hormone-releasing hormone (LH-RH) found in prostate cancers might be used for targeting of chemotherapeutic agents. Doxorubicin derivative 2-pyrrolinodoxorubicin (AN-201) can be linked to carrier analog [D-Lys6]LH-RH to form the targeted cytotoxic analog of LH- RH, AN-207. METHODS. We evaluated the effects of AN-207 and its components on the growth of LH-RH receptor-positive human prostate cancer PC-82 xenografted into nude mice. Analog AN-207, radical AN-201, carrier [D-Lys6]LH-RH, or a mixture of [D-Lys6]LH-RH and AN-201 were injected intravenously once at doses of 200 nmol/kg. Tumor growth, body weight, total WBC counts, and serum prostate-specific antigen (PSA) were determined. Receptors for LH-RH on PC- 82 tumors were evaluated, and the expression of mRNA for LH-RH receptors was assessed by RT-PCR. RESULTS. Eight weeks after administration of cytotoxic analog AN-207, there was a 67.8% reduction in tumor volume (P <0.01), 70.7% decrease in tumor burden (P <0.01), and 36.5% decrease in serum PSA levels (P <0.01) as compared with controls. Only one of 8 animals treated with AN- 207 died. Cytotoxic radical AN-201 caused a 34.2% (not significant, NS) reduction in tumor volume with no change in serum PSA, and killed 3 of 8 mice due to toxicity. Carrier [D-Lys6]LH-RH and the unconjugated mixture of [D- Lys6]LH-RH and AN-201 had no effect on tumor growth. LH-RH receptors as well as the expression of their mRNA were found in PC-82 tumors. CONCLUSIONS. The cytotoxic analog of LH-RH AN-207 powerfully inhibited growth of PC-82 human prostate cancer with only minor toxicity. Targeted cytotoxic LH-RH analogs may be useful for treatment of prostate cancer.

AB - BACKGROUND. Receptors for luteinizing hormone-releasing hormone (LH-RH) found in prostate cancers might be used for targeting of chemotherapeutic agents. Doxorubicin derivative 2-pyrrolinodoxorubicin (AN-201) can be linked to carrier analog [D-Lys6]LH-RH to form the targeted cytotoxic analog of LH- RH, AN-207. METHODS. We evaluated the effects of AN-207 and its components on the growth of LH-RH receptor-positive human prostate cancer PC-82 xenografted into nude mice. Analog AN-207, radical AN-201, carrier [D-Lys6]LH-RH, or a mixture of [D-Lys6]LH-RH and AN-201 were injected intravenously once at doses of 200 nmol/kg. Tumor growth, body weight, total WBC counts, and serum prostate-specific antigen (PSA) were determined. Receptors for LH-RH on PC- 82 tumors were evaluated, and the expression of mRNA for LH-RH receptors was assessed by RT-PCR. RESULTS. Eight weeks after administration of cytotoxic analog AN-207, there was a 67.8% reduction in tumor volume (P <0.01), 70.7% decrease in tumor burden (P <0.01), and 36.5% decrease in serum PSA levels (P <0.01) as compared with controls. Only one of 8 animals treated with AN- 207 died. Cytotoxic radical AN-201 caused a 34.2% (not significant, NS) reduction in tumor volume with no change in serum PSA, and killed 3 of 8 mice due to toxicity. Carrier [D-Lys6]LH-RH and the unconjugated mixture of [D- Lys6]LH-RH and AN-201 had no effect on tumor growth. LH-RH receptors as well as the expression of their mRNA were found in PC-82 tumors. CONCLUSIONS. The cytotoxic analog of LH-RH AN-207 powerfully inhibited growth of PC-82 human prostate cancer with only minor toxicity. Targeted cytotoxic LH-RH analogs may be useful for treatment of prostate cancer.

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