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Specific Antiproliferative Properties of Proteinaceous Toxin Secretions from the Marine Annelid Eulalia sp. onto Ovarian Cancer Cells
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Specific Antiproliferative Properties of Proteinaceous Toxin Secretions from the Marine Annelid Eulalia sp. onto Ovarian Cancer Cells
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Journal Article
Specific Antiproliferative Properties of Proteinaceous Toxin Secretions from the Marine Annelid Eulalia sp. onto Ovarian Cancer Cells
2021
Overview
As Yondelis joins the ranks of approved anti-cancer drugs, the benefit from exploring the oceans’ biodiversity becomes clear. From marine toxins, relevant bioproducts can be obtained due to their potential to interfere with specific pathways. We explored the cytotoxicity of toxin-bearing secretions of the polychaete Eulalia onto a battery of normal and cancer human cell lines and discovered that the cocktail of proteins is more toxic towards an ovarian cancer cell line (A2780). The secretions’ main proteins were identified by proteomics and transcriptomics: 14-3-3 protein, Hsp70, Rab3, Arylsulfatase B and serine protease, the latter two being known toxins. This mixture of toxins induces cell-cycle arrest at G2/M phase after 3h exposure in A2780 cells and extrinsic programmed cell death. These findings indicate that partial re-activation of the G2/M checkpoint, which is inactivated in many cancer cells, can be partly reversed by the toxic mixture. Protein–protein interaction networks partake in two cytotoxic effects: cell-cycle arrest with a link to RAB3C and RAF1; and lytic activity of arylsulfatases. The discovery of both mechanisms indicates that venomous mixtures may affect proliferating cells in a specific manner, highlighting the cocktails’ potential in the fine-tuning of anti-cancer therapeutics targeting cell cycle and protein homeostasis.
Publisher
MDPI AG,MDPI
Subject
/ Animals
/ Annelida
/ Antineoplastic Agents - isolation & purification
/ Antineoplastic Agents - pharmacology
/ Antineoplastic Agents - therapeutic use
/ Cancer
/ Cell Proliferation - drug effects
/ Cell Proliferation - physiology
/ Cell Survival - drug effects
/ Cells
/ DNA
/ Dose-Response Relationship, Drug
/ Eulalia
/ Female
/ Humans
/ Kinases
/ Marine Toxins - isolation & purification
/ Marine Toxins - pharmacology
/ Marine Toxins - therapeutic use
/ mixtures
/ Oceans
/ Ovarian Neoplasms - drug therapy
/ Ovarian Neoplasms - metabolism
/ Ovarian Neoplasms - pathology
/ Ovaries
/ protein-protein interactions
/ Proteins
/ Serine
/ Toxicity
/ toxin
/ Toxins
