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

K. Sugihara (), Y. Kobayashi, A. Suzuki, N. Tamura, K. Motamedchaboki, C.-T. Huang, T.O. Akama, J. Pecotte, P. Frost, C. Bauer, J.B. Jimenez, J. Nakayama, D. Aoki and M.N. Fukuda ()
Additional contact information
K. Sugihara: Hamamatsu University School of Medicine
Y. Kobayashi: Tumor Microenvironment, Cancer Center, Sanford-Burnham Medical Research Institute
A. Suzuki: Keio University School of Medicine
N. Tamura: Tumor Microenvironment, Cancer Center, Sanford-Burnham Medical Research Institute
K. Motamedchaboki: Tumor Microenvironment, Cancer Center, Sanford-Burnham Medical Research Institute
C.-T. Huang: Tumor Microenvironment, Cancer Center, Sanford-Burnham Medical Research Institute
T.O. Akama: Tumor Microenvironment, Cancer Center, Sanford-Burnham Medical Research Institute
J. Pecotte: Southwest National Primate Research Center, Texas Biomedical Research Institute
P. Frost: Southwest National Primate Research Center, Texas Biomedical Research Institute
C. Bauer: Southwest National Primate Research Center, Texas Biomedical Research Institute
J.B. Jimenez: Southwest National Primate Research Center, Texas Biomedical Research Institute
J. Nakayama: Shinshu University Graduate School of Medicine
D. Aoki: Keio University School of Medicine
M.N. Fukuda: Tumor Microenvironment, Cancer Center, Sanford-Burnham Medical Research Institute

Nature Communications, 2014, vol. 5, issue 1, 1-9

Abstract: Abstract 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.

Date: 2014
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DOI: 10.1038/ncomms5478

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