Effects of marine sponge extracts on mitogen-activated protein kinase (MAPK/ERK 1,2) activity in SW-13 human adrenal carcinoma cells

Some species of marine sponge have been shown to produce metabolites with endocrine-altering and cell growth regulatory properties. Since cell division and differentiation are controlled, in part, by the mitogen-activated protein kinase-extracellular signal-regulated kinase (MAPK/ERK) cascade, we tested extracts (1.0 mg/ml) from six shallow water marine species obtained in the Florida Keys for effects on MAPK/ERK l,2 (sub-variant of EC 2.7.1.37) activity in incubations with SW-13 human adrenal carcinoma cells in culture. In these short-term incubations, extracts from two species, the purple bleeding sponge ( Iotrochota birotulata) and the West Indian bath sponge ( Spongia barbara), significantly inhibited MAPK/ERK 1,2 activity (to 51 and 44% of control levels, respectively) without altering cell survival. Western blots for phosphorylated and total ERK showed that ERK 2 predominated over ERK 1 by a factor of about 4:1 and that the phosphorylated forms of these isozymes were strongly suppressed by active extracts from both sponges. Another species, the green sponge ( Haliclona veridis), whose extract has been shown previously to activate guanylate cyclase and to inhibit adenylate cyclase in a variety of mammalian tissues, was found not to affect MAPK/ERK 1,2 in human adrenal carcinoma cultures but did lyse and kill most of these cultured cells. Extracts from the sheepswool sponge ( Hippospongia lachne) and the bleeding sponge ( Oligoceras hemorrhages) did not significantly affect either MAPK/ERK 1,2 activity or the survival of attached cells. An extract from the fire sponge ( Tedania ignis) did not alter MAPK/ERK 1,2 activity but did modestly decrease cell viability. These studies document for the first time species-specifc effects of marine sponge extracts on the MAPK/ERK 1,2 cascade and on the growth and survival of human adrenal carcinoma cells in culture.