Kunitz type protease inhibitor EgKI-1 from the canine tapeworm Echinococcus granulosus as a promising therapeutic against breast cancer.

EgKI-1, a member of the Kunitz type protease inhibitor family, is highly expressed by the oncosphere of the canine tapeworm Echinococcus granulosus, the stage that is infectious to humans and ungulates, giving rise to a hydatid cyst localized to the liver and other organs. Larval protoscoleces, whic...

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Main Authors: Shiwanthi L Ranasinghe, Glen M Boyle, Katja Fischer, Jeremy Potriquet, Jason P Mulvenna, Donald P McManus
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2018-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC6118354?pdf=render
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spelling doaj-407c7ae2633e4bde9cd3aace055902f52020-11-24T20:41:39ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01138e020043310.1371/journal.pone.0200433Kunitz type protease inhibitor EgKI-1 from the canine tapeworm Echinococcus granulosus as a promising therapeutic against breast cancer.Shiwanthi L RanasingheGlen M BoyleKatja FischerJeremy PotriquetJason P MulvennaDonald P McManusEgKI-1, a member of the Kunitz type protease inhibitor family, is highly expressed by the oncosphere of the canine tapeworm Echinococcus granulosus, the stage that is infectious to humans and ungulates, giving rise to a hydatid cyst localized to the liver and other organs. Larval protoscoleces, which develop within the hydatid cyst, have been shown to possess anti-cancer properties, although the precise molecules involved have not been identified. We show that recombinant EgKI-1 inhibits the growth and migration of a range of human cancers including breast, melanoma and cervical cancer cell lines in a dose-dependent manner in vitro without affecting normal cell growth. Furthermore, EgKI-1 treatment arrested the cancer cell growth by disrupting the cell cycle and induced apoptosis of cancer cells in vitro. An in vivo model of triple negative breast cancer (MDA-MB-231) in BALB/c nude mice showed significant tumor growth reduction in EgKI-1-treated mice compared with controls. These findings indicate that EgKI-1 shows promise for future development as an anti-cancer therapeutic.http://europepmc.org/articles/PMC6118354?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Shiwanthi L Ranasinghe
Glen M Boyle
Katja Fischer
Jeremy Potriquet
Jason P Mulvenna
Donald P McManus
spellingShingle Shiwanthi L Ranasinghe
Glen M Boyle
Katja Fischer
Jeremy Potriquet
Jason P Mulvenna
Donald P McManus
Kunitz type protease inhibitor EgKI-1 from the canine tapeworm Echinococcus granulosus as a promising therapeutic against breast cancer.
PLoS ONE
author_facet Shiwanthi L Ranasinghe
Glen M Boyle
Katja Fischer
Jeremy Potriquet
Jason P Mulvenna
Donald P McManus
author_sort Shiwanthi L Ranasinghe
title Kunitz type protease inhibitor EgKI-1 from the canine tapeworm Echinococcus granulosus as a promising therapeutic against breast cancer.
title_short Kunitz type protease inhibitor EgKI-1 from the canine tapeworm Echinococcus granulosus as a promising therapeutic against breast cancer.
title_full Kunitz type protease inhibitor EgKI-1 from the canine tapeworm Echinococcus granulosus as a promising therapeutic against breast cancer.
title_fullStr Kunitz type protease inhibitor EgKI-1 from the canine tapeworm Echinococcus granulosus as a promising therapeutic against breast cancer.
title_full_unstemmed Kunitz type protease inhibitor EgKI-1 from the canine tapeworm Echinococcus granulosus as a promising therapeutic against breast cancer.
title_sort kunitz type protease inhibitor egki-1 from the canine tapeworm echinococcus granulosus as a promising therapeutic against breast cancer.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2018-01-01
description EgKI-1, a member of the Kunitz type protease inhibitor family, is highly expressed by the oncosphere of the canine tapeworm Echinococcus granulosus, the stage that is infectious to humans and ungulates, giving rise to a hydatid cyst localized to the liver and other organs. Larval protoscoleces, which develop within the hydatid cyst, have been shown to possess anti-cancer properties, although the precise molecules involved have not been identified. We show that recombinant EgKI-1 inhibits the growth and migration of a range of human cancers including breast, melanoma and cervical cancer cell lines in a dose-dependent manner in vitro without affecting normal cell growth. Furthermore, EgKI-1 treatment arrested the cancer cell growth by disrupting the cell cycle and induced apoptosis of cancer cells in vitro. An in vivo model of triple negative breast cancer (MDA-MB-231) in BALB/c nude mice showed significant tumor growth reduction in EgKI-1-treated mice compared with controls. These findings indicate that EgKI-1 shows promise for future development as an anti-cancer therapeutic.
url http://europepmc.org/articles/PMC6118354?pdf=render
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