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.
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Authors | Lilla Pethő, József Murányi, Kinga Pénzes, Bianka Gurbi, Diána Brauswetter, Gábor Halmos, Gabriella Csík, Gábor Mező |
Journal | International journal of molecular sciences
(Int J Mol Sci)
Vol. 20
Issue 20
(Oct 11 2019)
ISSN: 1422-0067 [Electronic] Switzerland |
PMID | 31614426
(Publication Type: Journal Article)
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Chemical References |
- GNRHR protein, human
- Peptides
- Protoporphyrins
- Receptors, LHRH
- Gonadotropin-Releasing Hormone
- protoporphyrin IX
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Topics |
- Adult
- Aged
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Cell Survival
(drug effects)
- Drug Screening Assays, Antitumor
- Female
- Gene Expression Regulation, Neoplastic
(drug effects)
- Gonadotropin-Releasing Hormone
(analogs & derivatives)
- Head and Neck Neoplasms
(drug therapy, metabolism)
- Humans
- Male
- Middle Aged
- Peptides
(administration & dosage, chemistry, pharmacology)
- Photochemotherapy
- Prognosis
- Protoporphyrins
(chemistry)
- Receptors, LHRH
(metabolism)
- Squamous Cell Carcinoma of Head and Neck
(drug therapy, metabolism)
- Survival Analysis
- Tissue Array Analysis
- Up-Regulation
(drug effects)
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