Salarin C, a member of the salarin superfamily of marine compounds, is a potent inducer of apoptosis.
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.
Ben-Califa
Nathalie
N
Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel.
Bishara
Ashgan
A
Kashman
Yoel
Y
Neumann
Drorit
D
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020014:K562 Cells; D018942:Macrolides / Q000494:pharmacology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D013997:Time Factors
D000970:Antineoplastic Agents; D018942:Macrolides; C571877:salarin C; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9