Identification and pharmaceutical evaluation of novel frog skin-derived serine proteinase inhibitor peptide–PE-BBI (Pelophylax esculentus Bowman-Birk inhibitor) for the potential treatment of cancer

Abstract Amphibian venom-derived peptides have high potential in the field of anticancer drug discovery. We have isolated a novel Bowman-Birk proteinase inhibitor (BBI)-type peptide from the skin secretion of Pelophylax esculentus (PE) named PE-BBI, and evaluated its bio-functions and anti-cancer ac...

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Autores principales:	Peng Lyu, Lilin Ge, Rui Ma, Ran Wei, Cian M. McCrudden, Tianbao Chen, Chris Shaw, Hang Fai Kwok
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Pelophylax Esculentus Bowman-Birk Protease Inhibitor (BBI) Skin Secretions Anti-cancer Ability Synthetic Replicates Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e47e647ee7894a52aaeccaa734ca8ee8
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spelling	oai:doaj.org-article:e47e647ee7894a52aaeccaa734ca8ee82021-12-02T15:07:57ZIdentification and pharmaceutical evaluation of novel frog skin-derived serine proteinase inhibitor peptide–PE-BBI (Pelophylax esculentus Bowman-Birk inhibitor) for the potential treatment of cancer10.1038/s41598-018-32947-52045-2322https://doaj.org/article/e47e647ee7894a52aaeccaa734ca8ee82018-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-32947-5https://doaj.org/toc/2045-2322Abstract Amphibian venom-derived peptides have high potential in the field of anticancer drug discovery. We have isolated a novel Bowman-Birk proteinase inhibitor (BBI)-type peptide from the skin secretion of Pelophylax esculentus (PE) named PE-BBI, and evaluated its bio-functions and anti-cancer activity in vitro. PE-BBI is a heptadecapeptide with C-terminal amidation. The mRNA sequence and primary structure of PE-BBI were identified using RT-PCR and LC/MS, respectively. A trypsin inhibitory assay was used to characterize the serine proteinase inhibitory activity of synthetic PE-BBI. PE-BBI’s myotropic activity was analyzed using isolated rat bladder and rat-tail artery smooth muscle tissues, and the anti-cancer ability of PE-BBI using human colorectal cancer cells. PE-BBI’s mechanism of action was investigated using Discovery studio software. PE-BBI showed trypsin inhibitory activity (Ki = 310 ± 72 nM), strong myotropic activity, and cytotoxicity that were specific to cancer cells, and no side effect to normal epithelial cells. The docking stimulation showed that PE-BBI had high affinity to several members of human kallikrein related peptidase (KLK) family. This finding helps to enrich our understanding of BBI peptides’ mode of action. Moreover, the data presented here validates frog secretions as sources of potential novel proteinase inhibitors for cancer treatment.Peng LyuLilin GeRui MaRan WeiCian M. McCruddenTianbao ChenChris ShawHang Fai KwokNature PortfolioarticlePelophylax EsculentusBowman-Birk Protease Inhibitor (BBI)Skin SecretionsAnti-cancer AbilitySynthetic ReplicatesMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-10 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Pelophylax Esculentus Bowman-Birk Protease Inhibitor (BBI) Skin Secretions Anti-cancer Ability Synthetic Replicates Medicine R Science Q
spellingShingle	Pelophylax Esculentus Bowman-Birk Protease Inhibitor (BBI) Skin Secretions Anti-cancer Ability Synthetic Replicates Medicine R Science Q Peng Lyu Lilin Ge Rui Ma Ran Wei Cian M. McCrudden Tianbao Chen Chris Shaw Hang Fai Kwok Identification and pharmaceutical evaluation of novel frog skin-derived serine proteinase inhibitor peptide–PE-BBI (Pelophylax esculentus Bowman-Birk inhibitor) for the potential treatment of cancer
description	Abstract Amphibian venom-derived peptides have high potential in the field of anticancer drug discovery. We have isolated a novel Bowman-Birk proteinase inhibitor (BBI)-type peptide from the skin secretion of Pelophylax esculentus (PE) named PE-BBI, and evaluated its bio-functions and anti-cancer activity in vitro. PE-BBI is a heptadecapeptide with C-terminal amidation. The mRNA sequence and primary structure of PE-BBI were identified using RT-PCR and LC/MS, respectively. A trypsin inhibitory assay was used to characterize the serine proteinase inhibitory activity of synthetic PE-BBI. PE-BBI’s myotropic activity was analyzed using isolated rat bladder and rat-tail artery smooth muscle tissues, and the anti-cancer ability of PE-BBI using human colorectal cancer cells. PE-BBI’s mechanism of action was investigated using Discovery studio software. PE-BBI showed trypsin inhibitory activity (Ki = 310 ± 72 nM), strong myotropic activity, and cytotoxicity that were specific to cancer cells, and no side effect to normal epithelial cells. The docking stimulation showed that PE-BBI had high affinity to several members of human kallikrein related peptidase (KLK) family. This finding helps to enrich our understanding of BBI peptides’ mode of action. Moreover, the data presented here validates frog secretions as sources of potential novel proteinase inhibitors for cancer treatment.
format	article
author	Peng Lyu Lilin Ge Rui Ma Ran Wei Cian M. McCrudden Tianbao Chen Chris Shaw Hang Fai Kwok
author_facet	Peng Lyu Lilin Ge Rui Ma Ran Wei Cian M. McCrudden Tianbao Chen Chris Shaw Hang Fai Kwok
author_sort	Peng Lyu
title	Identification and pharmaceutical evaluation of novel frog skin-derived serine proteinase inhibitor peptide–PE-BBI (Pelophylax esculentus Bowman-Birk inhibitor) for the potential treatment of cancer
title_short	Identification and pharmaceutical evaluation of novel frog skin-derived serine proteinase inhibitor peptide–PE-BBI (Pelophylax esculentus Bowman-Birk inhibitor) for the potential treatment of cancer
title_full	Identification and pharmaceutical evaluation of novel frog skin-derived serine proteinase inhibitor peptide–PE-BBI (Pelophylax esculentus Bowman-Birk inhibitor) for the potential treatment of cancer
title_fullStr	Identification and pharmaceutical evaluation of novel frog skin-derived serine proteinase inhibitor peptide–PE-BBI (Pelophylax esculentus Bowman-Birk inhibitor) for the potential treatment of cancer
title_full_unstemmed	Identification and pharmaceutical evaluation of novel frog skin-derived serine proteinase inhibitor peptide–PE-BBI (Pelophylax esculentus Bowman-Birk inhibitor) for the potential treatment of cancer
title_sort	identification and pharmaceutical evaluation of novel frog skin-derived serine proteinase inhibitor peptide–pe-bbi (pelophylax esculentus bowman-birk inhibitor) for the potential treatment of cancer
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/e47e647ee7894a52aaeccaa734ca8ee8
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Identification and pharmaceutical evaluation of novel frog skin-derived serine proteinase inhibitor peptide–PE-BBI (Pelophylax esculentus Bowman-Birk inhibitor) for the potential treatment of cancer

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