In this study the isolated compound 11-dehydrosinulariolide from soft coral
Sinularia leptoclados possessed anti-proliferative, anti-migratory and apoptosis-inducing
activities against A2058 melanoma cells. Anti-tumor effects of 11-dehydrosinulariolide
were determined by MTT assay, cell migration assay and flow cytometry. Growth
and migration of melanoma cells were dose-dependently inhibited by 2–8 μg/mL
11-dehydrosinulariolide. Flow cytometric data indicated that 11-dehydrosinulariolide
induces both early and late apoptosis in melanoma cells. It was found that the apoptosis
induced by 11-dehydrosinulariolide is relevant to mitochondrial-mediated apoptosis via
caspase-dependent pathways, elucidated by loss of mitochondrial membrane potential (ΔΨm),release of cytochrome C, activation of caspase-3/-9 and Bax as well as suppression of
Bcl-2/Bcl-xL. The cleavage of PARP-1 suggested partial involvement of caspase-independent
pathways. Immunoblotting data displayed up-regulations of PERK/eIF2α/ATF4/CHOP and
ATF6/CHOP coupling with elevation of ER stress chaperones GRP78, GRP94, calnexin,
calreticulin and PDI, implicating the involvement of these factors in ER stress-mediated
apoptosis induced by 11-dehydrosinulariolide. The abolishment of apoptotic events after
pre-treatment with salubrinal indicated that ER stress-mediated apoptosis is also induced
by 11-dehydrosinulariolide against melanoma cells. The data in this study suggest that
11-dehydrosinulariolide potentially induces apoptosis against melanoma cells via
mitochondrial dysregulation and ER stress pathways.
