Identification, purification and molecular characterization of chondrosin, a New Protein with anti-tumoral activity from the marine sponge Chondrosia Reniformis nardo 1847

Sonia Scarfì, Marina Pozzolini, Caterina Oliveri, Serena Mirata, Annalisa Salis, Gianluca Damonte, Daniela Fenoglio, Tiziana Altosole, Micha Ilan, Marco Bertolino, Marco Giovine*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Chondrosia reniformis is a common marine demosponge showing many peculiarities, lacking silica spicules and with a body entirely formed by a dense collagenous matrix. In this paper, we have described the identification of a new cytotoxic protein (chondrosin) with selective activity against specific tumor cell lines, from C. reniformis, collected from the Liguria Sea. Chondrosin was extracted and purified using a salting out approach and molecular weight size exclusion chromatography. The cytotoxic fractions were then characterized by two-dimensional gel electrophoresis and mass spectrometry analysis and matched the results with C. reniformis transcriptome database. The procedure allowed for identifying a full-length cDNA encoding for a 199-amino acids (aa) polypeptide, with a signal peptide of 21 amino acids. The mature protein has a theoretical molecular weight of 19611.12 and an IP of 5.11. Cell toxicity assays showed a selective action against some tumor cell lines (RAW 264.7 murine leukemia cells in particular). Cell death was determined by extracellular calcium intake, followed by cytoplasmic reactive oxygen species overproduction. The in silico modelling of chondrosin showed a high structural homology with the N-terminal region of the ryanodine receptor/channel and a short identity with defensin. The results are discussed suggesting a possible specific interaction of chondrosin with the Cav 1.3 ion voltage calcium channel expressed on the target cell membranes.

Original languageEnglish
Article number409
JournalMarine Drugs
Volume18
Issue number8
DOIs
StatePublished - 2020

Funding

FundersFunder number
Ministry of Foreign Affairs and International Cooperation of Italian Republic
Ministry of Science and Technology of the State of Israel
National Institute of Arthritis and Musculoskeletal and Skin DiseasesK08AR002018
Ministero dell’Istruzione, dell’Università e della Ricerca
Università degli Studi di Genova
Ministero degli Affari Esteri e della Cooperazione Internazionale

    Keywords

    • Chondrosia reniformis
    • Chondrosin
    • Cytotoxic protein
    • Marine toxin
    • Porifera

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