Salarin C, a member of the salarin superfamily of marine compounds, is a potent inducer of apoptosis

Nathalie Ben-Califa, Ashgan Bishara, Yoel Kashman, Drorit Neumann

Research output: Contribution to journalArticlepeer-review

Abstract

The continuous emergence of new diseases and the development of drug-resistant cancers necessitate the development of new drugs with novel mechanisms of action. The richest marine source of natural anti-cancer products has been soft-bodied organisms that lack physical defenses against their predators, and hence rely on chemical defense mechanisms using cytotoxic secondary metabolites. Bio-guided (brine shrimp test) separation of CHCl 3- CH 3OH (1:1) extract from the Madagascar Fascaplysinopsis sp. sponge provided several new compounds. Here we focused on the biological activity of a panel of novel natural compounds, salarins A-J. Of these, salarin C was the most potent inhibitor of proliferation, as demonstrated on the K562 leukemia cell line. Salarin C-treated K562 cells underwent apoptotic death as monitored by cell-cycle analysis, annexin V/propidium iodide staining, cleavage of poly-ADP-ribose polymerase (PARP) and caspase 3, and caspase 9 levels. The experimental approach described herein is an essential step towards identifying the cellular pathway(s) affected by salarin C and producing potent synthetic derivatives of salarin C with potential future uses as basic research tools and/or drugs and drug leads.

Original languageEnglish
Pages (from-to)98-104
Number of pages7
JournalInvestigational New Drugs
Volume30
Issue number1
DOIs
StatePublished - Feb 2012

Keywords

  • Apoptosis
  • Caspase
  • Cell cycle
  • K562 cells
  • Salarin C

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