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Comparative effects of aplysiatoxin, debromoaplysiatoxin, and teleocidin on receptor binding and phospholipid
Abstract:
We have compared the activities of aplysiatoxin and debromoaplysiatoxin, two polyacetate marine algae toxins, with teleocidin, a tumor-promoting indole alkaloid from Streptomyces, with respect to inhibition of specific binding of epidermal growth factor, and phorbol-12,13-dibutyrate to their respective receptors and ability to stimulate the release of radioactivity from cells prelabeled with choline or arachidonic acid. Although these compounds have chemical structures that are quite different from the phorbol esters, both aplysiatoxin and teleocidin are essentially equipotent with the potent tumor promoter 12-O-tetradecanoylphorbol-13-acetate in all four assays. The fact that aplysiatoxin and teleocidin inhibit phorbol-12,13-dibutyrate-receptor binding suggests that their biological activities are mediated by binding to the same receptors utilized by the phorbol esters. Debromoaplysiatoxin, a debrominated form of aplysiatoxin, is about 10-fold weaker than aplysiatoxin in inhibiting epidermal growth factor and phorbol-12,13-dibutyrate-receptor binding, but is equipotent with aplysiatoxin in stimulating the release of lipid metabolites from the prelabeled cells. The results are discussed in terms of possible heterogeneity of cellular receptors for this group of compounds.
Insights
Marine toxins aplysiatoxin and teleocidin, though structurally different, mimic phorbol ester tumor promoters by binding to the same receptors. This suggests shared biological pathways for these potent compounds.
Area of Science:
- Marine natural products chemistry
- Cellular signaling pathways
- Tumor promotion mechanisms
Background:
- Aplysiatoxin and debromoaplysiatoxin are marine algae polyacetate toxins.
- Teleocidin is a tumor-promoting indole alkaloid from Streptomyces.
- Phorbol esters are potent tumor promoters with known cellular receptors.
Purpose of the Study:
- To compare the biological activities of aplysiatoxin, debromoaplysiatoxin, and teleocidin.
- To investigate their effects on specific receptor binding and cellular metabolite release.
- To explore potential shared cellular receptors with phorbol esters.
Main Methods:
- Assays for inhibition of epidermal growth factor (EGF) receptor binding.
- Assays for inhibition of phorbol-12,13-dibutyrate (PDBu) receptor binding.
- Measurement of radioactivity release from cells prelabeled with choline or arachidonic acid.
Main Results:
- Aplysiatoxin and teleocidin were equipotent to 12-O-tetradecanoylphorbol-13-acetate (TPA) in all tested assays.
- These compounds inhibited PDBu-receptor binding, suggesting interaction with phorbol ester receptors.
- Debromoaplysiatoxin showed reduced receptor binding inhibition but retained metabolite release activity.
Conclusions:
- Aplysiatoxin and teleocidin likely exert their biological effects via phorbol ester receptors.
- Structural dissimilarity does not preclude shared receptor interactions and biological activities.
- Potential heterogeneity of cellular receptors for these compounds warrants further investigation.