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

• Published in: PloS one Vol. 13; no. 8; p. e0200433
• Main Authors: Ranasinghe, Shiwanthi L., Boyle, Glen M., Fischer, Katja, Potriquet, Jeremy, Mulvenna, Jason P., McManus, Donald P.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 31.08.2018; Public Library of Science (PLoS)
• Subjects: Anticancer properties; Apoptosis; Biology and Life Sciences; Breast cancer; Cancer; Cancer therapies; Cell cycle; Cervical cancer; Cervix; Cysts; Deoxyribonucleic acid; Disruption; DNA; Echinococcus granulosus; Immunology; Laboratories; Liver; Medical research; Medicine and Health Sciences; Melanoma; Mice; Molecular biology; Neutrophils; Organs; Parasites; Parasitology; Protease; Protease inhibitors; Proteinase inhibitors; Proteins; Research and Analysis Methods; Tumor cell lines; Tumors; Ungulates; Australia; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0200433

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.