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

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(3)OH (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.

• Authors: Nathalie Ben-Califa, Ashgan Bishara, Yoel Kashman, Drorit Neumann
• Journal: Investigational new drugs (Invest New Drugs) Vol. 30 Issue 1 Pg. 98-104 (Feb 2012) ISSN: 1573-0646 [Electronic] United States
• PMID: 20734109 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Macrolides
• salarin C
• Poly(ADP-ribose) Polymerases
• CASP3 protein, human
• CASP9 protein, human
• Caspase 3
• Caspase 9

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Caspase 3 (metabolism)
• Caspase 9 (metabolism)
• Cell Cycle (drug effects)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Dose-Response Relationship, Drug
• Humans
• K562 Cells
• Macrolides (pharmacology)
• Poly(ADP-ribose) Polymerases (metabolism)
• Time Factors