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Targeted proapoptotic LHRH-BH3 peptide.
Pharm Res. 2003 Jun; 20(6):889-96.PR

Abstract

PURPOSE

The purpose of this work was to construct and evaluate a novel targeted proapoptotic peptide for cancer treatment.

METHODS

The peptide consisted of luteinizing hormone-releasing hormone (LHRH) as a targeting moiety specific to LHRH receptors and a synthetic BCL-2 homology 3 (BH3) domain peptide as an apoptosis inducer and a suppressor of antiapoptotic cellular defense. Anticancer activity of the peptide was evaluated on different cancer cell lines.

RESULTS

The targeting receptor to LHRH peptide is overexpressed in several cancer cell lines but is not expressed in healthy human visceral organs. LHRH and BH3 peptides when applied separately did not demonstrate cellular toxicity. In contrast, the LHRH-BH3 peptide was toxic in several cancer cell lines. Coincubation of LHRH and LHRH-BH3 peptides significantly decreased cytotoxicity of the latter. It was found that the LHRH-BH3 peptide induced apoptosis by simultaneous inhibition of the antiapoptotic function of BCL-2 protein family and activation of caspase-dependent signaling pathway.

CONCLUSIONS

The proposed anticancer proapoptotic LHRH-BH3 peptide simultaneously affects two molecular targets: 1) extracellular cancer-specific LHRH receptors and 2) the intracellular controlling mechanisms of apoptosis. The results of this work may be used to design novel approaches for the treatment of various cancers.

Authors+Show Affiliations

Department of Pharmaceutics, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, New Jersey, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12817893

Citation

Dharap, Sonia S., and Tamara Minko. "Targeted Proapoptotic LHRH-BH3 Peptide." Pharmaceutical Research, vol. 20, no. 6, 2003, pp. 889-96.
Dharap SS, Minko T. Targeted proapoptotic LHRH-BH3 peptide. Pharm Res. 2003;20(6):889-96.
Dharap, S. S., & Minko, T. (2003). Targeted proapoptotic LHRH-BH3 peptide. Pharmaceutical Research, 20(6), 889-96.
Dharap SS, Minko T. Targeted Proapoptotic LHRH-BH3 Peptide. Pharm Res. 2003;20(6):889-96. PubMed PMID: 12817893.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Targeted proapoptotic LHRH-BH3 peptide. AU - Dharap,Sonia S, AU - Minko,Tamara, PY - 2003/6/24/pubmed PY - 2004/2/21/medline PY - 2003/6/24/entrez SP - 889 EP - 96 JF - Pharmaceutical research JO - Pharm Res VL - 20 IS - 6 N2 - PURPOSE: The purpose of this work was to construct and evaluate a novel targeted proapoptotic peptide for cancer treatment. METHODS: The peptide consisted of luteinizing hormone-releasing hormone (LHRH) as a targeting moiety specific to LHRH receptors and a synthetic BCL-2 homology 3 (BH3) domain peptide as an apoptosis inducer and a suppressor of antiapoptotic cellular defense. Anticancer activity of the peptide was evaluated on different cancer cell lines. RESULTS: The targeting receptor to LHRH peptide is overexpressed in several cancer cell lines but is not expressed in healthy human visceral organs. LHRH and BH3 peptides when applied separately did not demonstrate cellular toxicity. In contrast, the LHRH-BH3 peptide was toxic in several cancer cell lines. Coincubation of LHRH and LHRH-BH3 peptides significantly decreased cytotoxicity of the latter. It was found that the LHRH-BH3 peptide induced apoptosis by simultaneous inhibition of the antiapoptotic function of BCL-2 protein family and activation of caspase-dependent signaling pathway. CONCLUSIONS: The proposed anticancer proapoptotic LHRH-BH3 peptide simultaneously affects two molecular targets: 1) extracellular cancer-specific LHRH receptors and 2) the intracellular controlling mechanisms of apoptosis. The results of this work may be used to design novel approaches for the treatment of various cancers. SN - 0724-8741 UR - https://www.unboundmedicine.com/medline/citation/12817893/Targeted_proapoptotic_LHRH_BH3_peptide_ L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=12817893.ui DB - PRIME DP - Unbound Medicine ER -