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

PLoS One. 2018 Aug 31;13(8):e0200433. doi: 10.1371/journal.pone.0200433. eCollection 2018.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Breast Neoplasms / prevention & control*
  • Cell Cycle
  • Cell Movement*
  • Cell Proliferation*
  • Dogs
  • Echinococcus granulosus / chemistry*
  • Female
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Proteinase Inhibitory Proteins, Secretory / administration & dosage*
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Proteinase Inhibitory Proteins, Secretory

Grants and funding

This project was funded by program (APP1037304 to DPM) from the Australian National Health and Medical Research Council (NHMRC). DPM is a NHMRC Senior Principal Research Fellow and Senior Scientist at QIMR Berghofer.