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DOI: 10.1055/s-0033-1348572
Anti-Melanoma Activity of Stellettin A
In the course of searching for natural compounds that might have potential applications in the treatment of melanoma, stellettin A, an isomalabaricane triterpene from the marine sponge Geodia japonica, was found to inhibit the growth of melanoma cells by induction of abnormal protein glycosylation, endoplasmic reticulum (ER) stress and cell death. Stellettin A was cytotoxic to mouse melanoma B16F10 cells, with IC50= 0.15 µg/mL. Induction of ER chaperone GRP78 was demonstrated by both immunoblotting and immunofluorescence, indicating ER stress was activated after treatment with stellettin A for 24h. Down-regulation of B16F10 cell markers, TYR and TRP-1, was prominent at 0.6 µg/mL for 12 to 24h. In addition, aberrant glycosylation of TRP-1 starting at 12h after treatment with 0.6 µg/mL of stellettin A was demonstrated by endoglycosidase H. Stellettin A induced ER stress and autophagy in B16F10 cells, but neither decrease of anti-apoptotic protein Bcl-2 nor formation of apoptotic bodies was detected.