Spatane diterpenoids from the Hainan soft coral Sinularia nanolobata: emerging anticancer agents with c-MET...

Five previously undescribed spatane-type diterpenoids 1-5, one pair of previously unreported enantiomers 6 and 7, along with two known related compounds 8 and 9, have been isolated and characterized from the Hainan soft coral Sinularia nanolobata collected off Ximao Island in the South China Sea. Their structures were determined by extensive spectroscopic analysis, QM-NMR, TDDFT-ECD calculations, chemical conversion and comparison with those of related known compounds reported in literature. In bioassays, compounds 5 and 9 inhibited MDA-MB-231 cells proliferation with IC₅₀ values of 5.26 ± 0.68 and 22.2 ± 2.9 μM, respectively, while compounds 5-7 and 9 showed inhibitory effects against HT-29 cells with IC₅₀ values of 2.87 ± 1.48, 17.68 ± 0.39, 13.27 ± 3.56, and 29.19 ± 1.78 μM, respectively. Further investigation revealed that compound 5 induced S-phase arrest in HT-29 cells, promoted apoptosis through elevation of intracellular reactive oxygen species (ROS) and reduction of mitochondrial membrane potential. Combining a human RTK array kit with cellular protein and transcriptional analyses, demonstrated that the anticancer activity of 5 is closely related to the regulation of c-MET signaling pathways.