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Suitability of GnRH Receptors for Targeted Photodynamic Therapy in Head and Neck Cancers.
Int J Mol Sci 2019; 20(20)IJ

Abstract

Head and neck squamous cell carcinomas (HNSCC) have a high mortality rate, although several potential therapeutic targets have already been identified. Gonadotropin-releasing hormone receptor (GnRH-R) expression is less studied in head and neck cancers, hence, we investigated the therapeutic relevance of GnRH-R targeting in HNSCC patients. Our results indicate that half of the patient-derived samples showed high GnRH-R expression, which was associated with worse prognosis, making this receptor a promising target for GnRH-based drug delivery. Photodynamic therapy is a clinically approved treatment for HNSCC, and the efficacy and selectivity may be enhanced by the covalent conjugation of the photosensitizer to a GnRH-R targeting peptide. Several native ligands, gonadotropin-releasing hormone (GnRH) isoforms, are known to target GnRH-R effectively. Therefore, different 4Lys(Bu) modified GnRH analogs were designed and conjugated to protoporphyrin IX. The receptor binding potency of the novel conjugates was measured on human pituitary and human prostate cancer cells, indicating only slightly lower GnRH-R affinity than the peptides. The in vitro cell viability inhibition was tested on Detroit-562 human pharyngeal carcinoma cells that express GnRH-R in high levels, and the results showed that all conjugates were more effective than the free protoporphyrin IX.

Authors+Show Affiliations

MTA-ELTE Research Group of Peptide Chemistry, 1117 Budapest, Hungary. lilla.petho@chem.elte.hu.MTA-SE Pathobiochemistry Research Group, 1094 Budapest, Hungary. jozsefmuranyi84@gmail.com.MTA-SE Pathobiochemistry Research Group, 1094 Budapest, Hungary. penzes.kinga@med.semmelweis-univ.hu.MTA-SE Pathobiochemistry Research Group, 1094 Budapest, Hungary. gurbi.bianka@med.semmelweis-univ.hu.MTA-SE Pathobiochemistry Research Group, 1094 Budapest, Hungary. brauswetter.diana@med.semmelweis-univ.hu.Department of Biopharmacy, Faculty of Pharmacy, University of Debrecen, 4032 Debrecen, Hungary. halmos.gabor@pharm.unideb.hu.SE Department of Biophysics and Radiation Biology, 1094 Budapest, Hungary. csik.gabriella@med.semmelweis-univ.hu.MTA-ELTE Research Group of Peptide Chemistry, 1117 Budapest, Hungary. gmezo@elte.hu. Department of Organic Chemistry, Faculty of Science, Institute of Chemistry, ELTE Eötvös Loránd University, 1117 Budapest, Hungary. gmezo@elte.hu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31614426

Citation

Pethő, Lilla, et al. "Suitability of GnRH Receptors for Targeted Photodynamic Therapy in Head and Neck Cancers." International Journal of Molecular Sciences, vol. 20, no. 20, 2019.
Pethő L, Murányi J, Pénzes K, et al. Suitability of GnRH Receptors for Targeted Photodynamic Therapy in Head and Neck Cancers. Int J Mol Sci. 2019;20(20).
Pethő, L., Murányi, J., Pénzes, K., Gurbi, B., Brauswetter, D., Halmos, G., ... Mező, G. (2019). Suitability of GnRH Receptors for Targeted Photodynamic Therapy in Head and Neck Cancers. International Journal of Molecular Sciences, 20(20), doi:10.3390/ijms20205027.
Pethő L, et al. Suitability of GnRH Receptors for Targeted Photodynamic Therapy in Head and Neck Cancers. Int J Mol Sci. 2019 Oct 11;20(20) PubMed PMID: 31614426.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Suitability of GnRH Receptors for Targeted Photodynamic Therapy in Head and Neck Cancers. AU - Pethő,Lilla, AU - Murányi,József, AU - Pénzes,Kinga, AU - Gurbi,Bianka, AU - Brauswetter,Diána, AU - Halmos,Gábor, AU - Csík,Gabriella, AU - Mező,Gábor, Y1 - 2019/10/11/ PY - 2019/07/26/received PY - 2019/10/02/revised PY - 2019/10/08/accepted PY - 2019/10/17/entrez PY - 2019/10/17/pubmed PY - 2019/10/17/medline KW - GnRH KW - GnRH-R KW - conjugate KW - head and neck cancer KW - photodynamic therapy KW - protoporphyrin KW - targeted drug delivery JF - International journal of molecular sciences JO - Int J Mol Sci VL - 20 IS - 20 N2 - Head and neck squamous cell carcinomas (HNSCC) have a high mortality rate, although several potential therapeutic targets have already been identified. Gonadotropin-releasing hormone receptor (GnRH-R) expression is less studied in head and neck cancers, hence, we investigated the therapeutic relevance of GnRH-R targeting in HNSCC patients. Our results indicate that half of the patient-derived samples showed high GnRH-R expression, which was associated with worse prognosis, making this receptor a promising target for GnRH-based drug delivery. Photodynamic therapy is a clinically approved treatment for HNSCC, and the efficacy and selectivity may be enhanced by the covalent conjugation of the photosensitizer to a GnRH-R targeting peptide. Several native ligands, gonadotropin-releasing hormone (GnRH) isoforms, are known to target GnRH-R effectively. Therefore, different 4Lys(Bu) modified GnRH analogs were designed and conjugated to protoporphyrin IX. The receptor binding potency of the novel conjugates was measured on human pituitary and human prostate cancer cells, indicating only slightly lower GnRH-R affinity than the peptides. The in vitro cell viability inhibition was tested on Detroit-562 human pharyngeal carcinoma cells that express GnRH-R in high levels, and the results showed that all conjugates were more effective than the free protoporphyrin IX. SN - 1422-0067 UR - https://www.unboundmedicine.com/medline/citation/31614426/Suitability_of_GnRH_Receptors_for_Targeted_Photodynamic_Therapy_in_Head_and_Neck_Cancers L2 - http://www.mdpi.com/resolver?pii=ijms20205027 DB - PRIME DP - Unbound Medicine ER -