Journal Article

Development of pro-apoptotic peptides as potential therapy for peritoneal endometriosis

Nakayama, J., Sugihara, K., Bauer, C., Kobayashi, Y., Tamura, N., Suzuki, A., Pecotte, J., Frost, P., Fukuda, M.N., Akama, T.O., Motamedchaboki, K., Jimenez, J.B., Huang, C.-T., Aoki, D.

2014

Overview

Endometriosis is a common gynaecological disease associated with pelvic pain and infertility. Current treatments include oral contraceptives combined with nonsteroidal anti-inflammatory drugs or surgery to remove lesions, all of which provide a temporary but not complete cure. Here we identify an endometriosis-targeting peptide that is internalized by cells, designated z13, using phage display. As most endometriosis occurs on organ surfaces facing the peritoneum, we subtracted a phage display library with female mouse peritoneum tissue and selected phage clones by binding to human endometrial epithelial cells. Proteomics analysis revealed the z13 receptor as the cyclic nucleotide-gated channel β3, a sorting pathway protein. We then linked z13 with an apoptosis-inducing peptide and with an endosome-escaping peptide. When these peptides were co-administered into the peritoneum of baboons with endometriosis, cells in lesions selectively underwent apoptosis with no effect on neighbouring organs. Thus, this study presents a strategy that could be useful to treat peritoneal endometriosis in humans. Endometriosis is a painful condition in which endometrial cells are found outside the womb. Here, the authors identify a peptide that specifically binds to a receptor expressed on endometrial epithelial cells and use it to induce apoptosis in both cultured cells and baboons with endometriosis.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Pub. Group
• Subject: 42/109 / 692/308 / 692/699/2768 / 692/700/565/1331 / 82 / 82/58 / Amino Acid Sequence / Animals / Anti-inflammatory agents / Apoptosis / Apoptosis - drug effects / Cancer / Cloning / Contraceptives / Cyclic Nucleotide-Gated Cation Channels - metabolism / Disease Models, Animal / DNA-Binding Proteins - metabolism / Drug Evaluation, Preclinical - methods / Endometriosis / Endometriosis - drug therapy / Endometriosis - pathology / Endometrium - pathology / Epithelial Cells - metabolism / Female / Gynecology / Humanities and Social Sciences / Humans / Infertility / Lesions / Libraries / Mice, Inbred C57BL / Molecular Sequence Data / Molecular Targeted Therapy - methods / multidisciplinary / Nonsteroidal anti-inflammatory drugs / Obstetrics / Papio / Peptide Library / Peptides / Peptides - metabolism / Peptides - pharmacology / Peritoneal Diseases - drug therapy / Peritoneal Diseases - pathology / Primates / Science / Science (multidisciplinary) / Steroids / Surgery