Specific Antiproliferative Properties of Proteinaceous Toxin Secretions from the Marine Annelid Eulalia sp. onto Ovarian Cancer Cells

Abstract

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.

Cytotoxicity Studies of the Crude venom and Fractions of Persian Gulf Snail (Conus Textile) on Chronic Lymphocytic Leukemia and Normal Lymphocytes

“…Initially, the results showed that the crude venom and its fraction B had the ability to reduce the viability of CLL B-lymphocytes. These results are in agreement with previous studies that have shown that the use of venoms extracted from marine animals is associated with a decrease in the viability of various cancer cell lines (Catanesi et al, 2021;Rodrigo et al, 2021). Studies have shown that there is an inverse relationship between cell viability and apoptotic signaling (Li et al, 2020;Wang et al, 2020).…”

Aggregation versus Biological Activity in Gold(I) Complexes. An Unexplored Concept

“…After 0 h, 30 min, 1 h, 3 h, or 6 h of incubation, the cells were fixed with 4% (w/v) formaldehyde (Sigma-Aldrich, Merck, Kenilworth, NJ) for 15 min and washed three times with PBS. The cell membrane was then disrupted by a 5 min incubation with 0.1% (v/v) Triton (Sigma-Aldrich, Merck) and washed three times with PBS, and the cells were incubated for 30 min with 1% (w/v) bovine serum albumin (BSA; NZYtech, Lisbon, Portugal) and 20 min with AlexaFluor 488 phalloidin (Invitrogen, ThermoFisher Scientific), as previously described . After washing three times with PBS, the cells were visualized with an Eclipse Ti–U inverted microscope with a green filter cube (an excitation filter range at 465–495 nm and an emission filter range at 515–555 nm), and images were acquired with the respective microscope software.…”

“…The cell membrane was then disrupted by a 5 min incubation with 0.1% (v/v) Triton (Sigma-Aldrich, Merck) and washed three times with PBS, and the cells were incubated for 30 min with 1% (w/v) bovine serum albumin (BSA; NZYtech, Lisbon, Portugal) and 20 min with AlexaFluor 488 phalloidin (Invitrogen, ThermoFisher Scientific), as previously described. 71 After washing three times with PBS, the cells were visualized with an Eclipse Ti−U inverted microscope with a green filter cube (an excitation filter range at 465−495 nm and an emission filter range at 515−555 nm), and images were acquired with the respective microscope software. Three different images with around 20 cells were acquired per sample with a 40× objective, or five different images with around five cells were acquired with a 100× objective.…”

Marine Organisms as a Rich Source of Biologically Active Peptides

“…The combination of transcriptomics and proteomics research over the past few years has also resulted in significant advances in the identification of potential drugs from marine toxins, while improvements in liquid chromatography-tandem mass spectrometry made this task more achievable (Xie et al, 2017). The importance of research in this area can be exemplified by the identification of bioproducts capable of interfering with specific pathways, allowing the development of anti-cancer treatments (Rodrigo et al, 2021). Rodrigo et al (2021) discovered that a cocktail of proteins from Eulalia sp.…”

“…The importance of research in this area can be exemplified by the identification of bioproducts capable of interfering with specific pathways, allowing the development of anti-cancer treatments (Rodrigo et al, 2021). Rodrigo et al (2021) discovered that a cocktail of proteins from Eulalia sp. is more toxic toward an ovarian cell line (A2780), supporting the potential of mixed proteins in venoms against aggressively proliferating cells.…”