K092A and K092B, Two Peptides Isolated from the Dogfish (Scyliorhinus canicula L.), with Potential Antineoplastic Activity Against Human Prostate and Breast Cancer Cells.

Adrien Bosseboeuf,Amandine Baron,Pierrick Auvray,Elise Duval,Aude Gautier,Pascal Sourdaine

doi:10.3390/md17120672

Abstract

Cancer therapy is currently a major challenge within the research community, especially in reducing the side effects of treatments and to develop new specific strategies against cancers that still have a poor prognosis. In this context, alternative strategies using biotechnologies, such as marine peptides, have been developed based on their promise of effectivity associated with a low toxicity for healthy cells. The purpose of the present paper is to investigate the active mechanism of two peptides that were isolated from the epigonal tissue of the lesser spotted dogfish Scyliorhinus canicula L., identified NFDTDEQALEDVFSKYG (K092A) and EAPPEAAEEDEW (K092B) on the in vitro growth inhibition of ZR-75-1 mammary carcinoma cells and MDA-Pca-2b prostate cancer cells. The effects of the peptides on cell proliferation and cell death mechanisms were studied by the flow cytometry and immunofluorescence microscopy approaches. The results have shown the onset of both K092A- and K092B-induced early cytoskeleton changes, and then cell cycle perturbations followed by non-apoptotic cell death. Moreover, impedance perturbation and plasma membrane perforation in ZR-75-1 K092A-treated cell cultures and autophagy inhibition in MDA-Pca-2b K092B-treated cells have been observed. In conclusion, these two bioactive peptides from dogfish exhibit antineoplastic activity on the human prostate and breast cancer cells in vitro.

Highlights

Bioactive peptides are promising for therapeutic use due to several advantages: they are of small size and often constitute the functional part of proteins and, they are highly functionally efficient, synthesized, and modified to enhance their properties; they often target cancer cells without damaging normal cells; they do not accumulate in specific organs; and, their degradation generates amino acids, which minimizes their toxicity and side effects and they are not usually genotoxic [1,2,3]
We have shown that peptides that were isolated from male genital tract of the lesser spotted dogfish Scyliorhinus canicula presented a dose-dependent antineoplastic activity on various human cancer cell lines [33]
This study reported that the first noticeable effects of K092B on MDA-Pca-2b cells, as observed at 6 hpt, consisted of: a cytostatic effect that was observed by real-time electric impedance sensing measurements, autophagy inhibition, and cytoskeleton aggregation

Summary

Introduction

Bioactive peptides are promising for therapeutic use due to several advantages: they are of small size and often constitute the functional part of proteins and, they are highly functionally efficient, synthesized, and modified to enhance their properties; they often target cancer cells without damaging normal cells; they do not accumulate in specific organs; and, their degradation generates amino acids, which minimizes their toxicity and side effects and they are not usually genotoxic [1,2,3]. Several binding peptides can be used as chemotherapy- or nanoparticles- carriers for targeted drug delivery in cancer therapy due to their strong ability to target and bind specific proteins [8]

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