Kinase-Based Screening of Marine Natural Extracts Leads to the Identification of a Cytotoxic High Molecular Weight Metabolite from the Mediterranean Sponge Crambe tailliezi

Mar Drugs. 2019 Oct 9;17(10):569. doi: 10.3390/md17100569.

Abstract

Regulated cell death (RCD) results from the activation of one or more signal transduction modules both in physiological or pathological conditions. It is now established that RCD is involved in numerous human diseases, including cancer. As regulated cell death processes can be modulated by pharmacological tools, the research reported here aims to characterize new marine compounds acting as RCD modulators. Protein kinases (PKs) are key signaling actors in various RCDs notably through the control of either mitosis (e.g., the PKs Aurora A and B) or necroptosis (e.g., RIPK1 and RIPK3). From the primary screening of 27 various extracts of marine organisms collected in the Mediterranean Sea, an extract and subsequently a purified high molecular weight compound dubbed P3, were isolated from the marine sponge Crambe tailliezi and characterized as a selective inhibitor of PKs Aurora A and B. Furthermore, P3 was shown to induce apoptosis and to decrease proliferation and mitotic index of human osteosarcoma U-2 OS cells.

Keywords: Crambe tailliezi; RIP1-independent cell death; Screening; kinase inhibition; marine natural products; regulated cell death.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Biological Products / pharmacology*
  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Crambe Sponge / chemistry*
  • Crambe Sponge / metabolism*
  • Cytotoxins / pharmacology*
  • HEK293 Cells
  • Hep G2 Cells
  • Humans
  • MCF-7 Cells
  • Mediterranean Sea
  • Molecular Weight
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinases / metabolism
  • Signal Transduction / drug effects

Substances

  • Biological Products
  • Cytotoxins
  • Protein Kinase Inhibitors
  • Protein Kinases