Targeting of cytotoxic bombesin analog AN-215 to H-69 small cell lung carcinoma as demonstrated by semi-quantitative microsatellite analysis in vitro

H. Kiaris, Andrew V Schally, A. Nagy, P. Armatis

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Targeting of cytotoxic peptide analogs represents a modern approach to cancer chemotherapy because it greatly reduces peripheral toxicity. Recently, we developed a powerful cytotoxic analog of bombesin, AN-215, consisting of the superactive derivative of doxorubicin (DOX), 2-pyrrolino-DOX (AN-201) linked to the bombesin-like carrier peptide Gln-Trp-Ala-Val-Gly-His-Leu- ψ(CH2-NH)-Leu-NH2. This cytotoxic analog of bombesin was designed to be targeted to tumors that express bombesin receptors, such as small cell lung carcinoma (SCLC). In the present study we investigated whether targeting of AN-215 to bombesin receptor-positive cell line, such as NCI-H-69 SCLC, in the presence of the bombesin receptor-negative non-SCLC cell line NCI-H-157, could be demonstrated in vitro by semi-quantitative polymerase chain reaction (PCR) amplification of microsatellite markers. NCI-H-69 cells were co- cultured in vitro with NCI-H-157 non-SCLC cells and exposed to 5 nM AN-215 or AN-201 for 4 h. Untreated cells were used as controls. The cells were then cultured for 4 days in the absence of cytotoxic agents and genomic DNA was extracted for microsatellite analysis with the marker D8S264 for which specific alleles for each cell line could be identified. Semi-quantitative analysis of the intensity of the alleles that correspond to each cell line indicated that AN-201 has no selectivity for any of the cell lines, while AN- 215 was targeted specifically to H-69 cells. Thus, cytotoxic bombesin analog AN-215 can be targeted to tumors that express bombesin receptors, such as SCLC. Assays based on the co-culture of heterogeneous cell populations followed by microsatellite analysis may be useful for initial screening of targeted cytotoxic analogs.

Original languageEnglish
Pages (from-to)266-270
Number of pages5
JournalTumor Targeting
Volume4
Issue number4
StatePublished - Dec 1 1999
Externally publishedYes

Fingerprint

Bombesin
Small Cell Lung Carcinoma
Bombesin Receptors
Microsatellite Repeats
Cell Line
Non-Small Cell Lung Carcinoma
Doxorubicin
Alleles
Neoplasms
Peptides
Cytotoxins
Coculture Techniques
In Vitro Techniques
AN 215
Drug Therapy
Polymerase Chain Reaction
DNA
Population
AN 204

Keywords

  • Cancer therapy
  • Genetic heterogeneity
  • H-157
  • Microsatellite markers
  • SCLC
  • Semi-quantitative PCR
  • Targeted cytotoxic analogs

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology

Cite this

Targeting of cytotoxic bombesin analog AN-215 to H-69 small cell lung carcinoma as demonstrated by semi-quantitative microsatellite analysis in vitro. / Kiaris, H.; Schally, Andrew V; Nagy, A.; Armatis, P.

In: Tumor Targeting, Vol. 4, No. 4, 01.12.1999, p. 266-270.

Research output: Contribution to journalArticle

@article{6bf902bd3da348899e5685520dd0501c,
title = "Targeting of cytotoxic bombesin analog AN-215 to H-69 small cell lung carcinoma as demonstrated by semi-quantitative microsatellite analysis in vitro",
abstract = "Targeting of cytotoxic peptide analogs represents a modern approach to cancer chemotherapy because it greatly reduces peripheral toxicity. Recently, we developed a powerful cytotoxic analog of bombesin, AN-215, consisting of the superactive derivative of doxorubicin (DOX), 2-pyrrolino-DOX (AN-201) linked to the bombesin-like carrier peptide Gln-Trp-Ala-Val-Gly-His-Leu- ψ(CH2-NH)-Leu-NH2. This cytotoxic analog of bombesin was designed to be targeted to tumors that express bombesin receptors, such as small cell lung carcinoma (SCLC). In the present study we investigated whether targeting of AN-215 to bombesin receptor-positive cell line, such as NCI-H-69 SCLC, in the presence of the bombesin receptor-negative non-SCLC cell line NCI-H-157, could be demonstrated in vitro by semi-quantitative polymerase chain reaction (PCR) amplification of microsatellite markers. NCI-H-69 cells were co- cultured in vitro with NCI-H-157 non-SCLC cells and exposed to 5 nM AN-215 or AN-201 for 4 h. Untreated cells were used as controls. The cells were then cultured for 4 days in the absence of cytotoxic agents and genomic DNA was extracted for microsatellite analysis with the marker D8S264 for which specific alleles for each cell line could be identified. Semi-quantitative analysis of the intensity of the alleles that correspond to each cell line indicated that AN-201 has no selectivity for any of the cell lines, while AN- 215 was targeted specifically to H-69 cells. Thus, cytotoxic bombesin analog AN-215 can be targeted to tumors that express bombesin receptors, such as SCLC. Assays based on the co-culture of heterogeneous cell populations followed by microsatellite analysis may be useful for initial screening of targeted cytotoxic analogs.",
keywords = "Cancer therapy, Genetic heterogeneity, H-157, Microsatellite markers, SCLC, Semi-quantitative PCR, Targeted cytotoxic analogs",
author = "H. Kiaris and Schally, {Andrew V} and A. Nagy and P. Armatis",
year = "1999",
month = "12",
day = "1",
language = "English",
volume = "4",
pages = "266--270",
journal = "Tumor Targeting",
issn = "1351-8488",
publisher = "Stockton Press",
number = "4",

}

TY - JOUR

T1 - Targeting of cytotoxic bombesin analog AN-215 to H-69 small cell lung carcinoma as demonstrated by semi-quantitative microsatellite analysis in vitro

AU - Kiaris, H.

AU - Schally, Andrew V

AU - Nagy, A.

AU - Armatis, P.

PY - 1999/12/1

Y1 - 1999/12/1

N2 - Targeting of cytotoxic peptide analogs represents a modern approach to cancer chemotherapy because it greatly reduces peripheral toxicity. Recently, we developed a powerful cytotoxic analog of bombesin, AN-215, consisting of the superactive derivative of doxorubicin (DOX), 2-pyrrolino-DOX (AN-201) linked to the bombesin-like carrier peptide Gln-Trp-Ala-Val-Gly-His-Leu- ψ(CH2-NH)-Leu-NH2. This cytotoxic analog of bombesin was designed to be targeted to tumors that express bombesin receptors, such as small cell lung carcinoma (SCLC). In the present study we investigated whether targeting of AN-215 to bombesin receptor-positive cell line, such as NCI-H-69 SCLC, in the presence of the bombesin receptor-negative non-SCLC cell line NCI-H-157, could be demonstrated in vitro by semi-quantitative polymerase chain reaction (PCR) amplification of microsatellite markers. NCI-H-69 cells were co- cultured in vitro with NCI-H-157 non-SCLC cells and exposed to 5 nM AN-215 or AN-201 for 4 h. Untreated cells were used as controls. The cells were then cultured for 4 days in the absence of cytotoxic agents and genomic DNA was extracted for microsatellite analysis with the marker D8S264 for which specific alleles for each cell line could be identified. Semi-quantitative analysis of the intensity of the alleles that correspond to each cell line indicated that AN-201 has no selectivity for any of the cell lines, while AN- 215 was targeted specifically to H-69 cells. Thus, cytotoxic bombesin analog AN-215 can be targeted to tumors that express bombesin receptors, such as SCLC. Assays based on the co-culture of heterogeneous cell populations followed by microsatellite analysis may be useful for initial screening of targeted cytotoxic analogs.

AB - Targeting of cytotoxic peptide analogs represents a modern approach to cancer chemotherapy because it greatly reduces peripheral toxicity. Recently, we developed a powerful cytotoxic analog of bombesin, AN-215, consisting of the superactive derivative of doxorubicin (DOX), 2-pyrrolino-DOX (AN-201) linked to the bombesin-like carrier peptide Gln-Trp-Ala-Val-Gly-His-Leu- ψ(CH2-NH)-Leu-NH2. This cytotoxic analog of bombesin was designed to be targeted to tumors that express bombesin receptors, such as small cell lung carcinoma (SCLC). In the present study we investigated whether targeting of AN-215 to bombesin receptor-positive cell line, such as NCI-H-69 SCLC, in the presence of the bombesin receptor-negative non-SCLC cell line NCI-H-157, could be demonstrated in vitro by semi-quantitative polymerase chain reaction (PCR) amplification of microsatellite markers. NCI-H-69 cells were co- cultured in vitro with NCI-H-157 non-SCLC cells and exposed to 5 nM AN-215 or AN-201 for 4 h. Untreated cells were used as controls. The cells were then cultured for 4 days in the absence of cytotoxic agents and genomic DNA was extracted for microsatellite analysis with the marker D8S264 for which specific alleles for each cell line could be identified. Semi-quantitative analysis of the intensity of the alleles that correspond to each cell line indicated that AN-201 has no selectivity for any of the cell lines, while AN- 215 was targeted specifically to H-69 cells. Thus, cytotoxic bombesin analog AN-215 can be targeted to tumors that express bombesin receptors, such as SCLC. Assays based on the co-culture of heterogeneous cell populations followed by microsatellite analysis may be useful for initial screening of targeted cytotoxic analogs.

KW - Cancer therapy

KW - Genetic heterogeneity

KW - H-157

KW - Microsatellite markers

KW - SCLC

KW - Semi-quantitative PCR

KW - Targeted cytotoxic analogs

UR - http://www.scopus.com/inward/record.url?scp=0033508030&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033508030&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:0033508030

VL - 4

SP - 266

EP - 270

JO - Tumor Targeting

JF - Tumor Targeting

SN - 1351-8488

IS - 4

ER -