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.
Highlights
Protein-based therapeutics enable targeted approaches for treating cancer [1]
The protein had substantially less effect on the growth of primary neonatal foreskin fibroblast (NFF) cells, and had ~9–40 fold high inhibit cell growth by 50% (IC50) value compared with the IC50 values of tested human cancer cell lines
The observed inhibition of cancer cell migration by EgKI-1 is an important aspect to consider for cancer therapeutic development
Summary
Protein-based therapeutics enable targeted approaches for treating cancer [1]. There are many benefits of proteins over small-molecule drugs mainly because of the increased surface area accessing a much wider range of protein targets [2]. Protease inhibitors are important as potential cancer therapeutics as proteases are associated with carcinogenesis and cancer progression. Numerous plant protease inhibitors have recently entered human clinical trials [3]. Parasites produce a range of protease inhibitors with diverse functions mainly to evade hostile adverse host reactions [4]. Several parasites, including the liver flukes, Opisthorchis viverrini and Clonorchis sinensis, and the blood fluke, Schistosoma haematobium, are known risk factors for cholangiocarcinoma and bladder cancer, respectively [5].
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