Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Bioactive Properties of Venoms Isolated from Whiptail Stingrays and the Search for Molecular Mechanisms and Targets

Version 1 : Received: 28 February 2024 / Approved: 29 February 2024 / Online: 29 February 2024 (11:41:25 CET)

A peer-reviewed article of this Preprint also exists.

Doupnik, C.A.; Luer, C.A.; Walsh, C.J.; Restivo, J.; Brick, J.X. Bioactive Properties of Venoms Isolated from Whiptail Stingrays and the Search for Molecular Mechanisms and Targets. Pharmaceuticals 2024, 17, 488. Doupnik, C.A.; Luer, C.A.; Walsh, C.J.; Restivo, J.; Brick, J.X. Bioactive Properties of Venoms Isolated from Whiptail Stingrays and the Search for Molecular Mechanisms and Targets. Pharmaceuticals 2024, 17, 488.

Abstract

Abstract: The venom-containing barb attached to their ‘whip-like’ tail provides stingrays a defensive mechanism for evading predators such as sharks. From human encounters, dermal stingray envenomation is characterized by intense pain often followed by tissue necrosis occurring over several days to several weeks. The bioactive components in stingray venoms (SRV’s) and their molecular targets and mechanisms that mediate these complex responses are not well understood. Given the utility of venom-derived proteins from other venomous species for biomedical and pharmaceutical applications, we set out to characterize the bioactivity of SRV from three local species that belong to the Dasyatoidea ‘whiptail’ superfamily. Multiple cell-based assays were used to quantify and compare the in vitro effects of these SRV’s on different cell lines. All three SRV’s demonstrated concentration-dependent growth inhibitory effects on three different human cell lines tested. In contrast, a mouse fibrosarcoma cell line was markedly resistant to all three SRV’s, indicating the molecular target(s) for mediating the SRV effects are not expressed on these cells. The multifunctional SRV responses were characterized by an acute disruption of cell adhesion leading to apoptosis. These findings aim to guide future investigations of identified SRV proteins and their molecular targets for potential use in biomedical applications.

Keywords

apoptosis; cell adhesion; cell growth; fibrosarcoma; galectin-like proteins; stingray; toxin; venom

Subject

Medicine and Pharmacology, Pharmacology and Toxicology

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