BACKGROUND AND PURPOSE:
Marine sponges have evolved the capacity to produce a series of very efficient chemicals to combat virus, bacteria, and eukariotic organisms. It has been demonstrated that several of these compounds have anti-neoplastic activity. The highly toxic sponge Crambe crambe has been the source of several molecules named crambescidins. Of these, crambescidin-816 has been shown to be cytotoxic for colon carcinoma cells. To further investigate the potential anti-carcinogenic effect of crambescidin-816, we analyzed the effect of this compound on transcription of HepG2 cells by microarray analysis followed by experiments guided by the results obtained.
EXPERIMENTAL APPROACH:
After cytotoxicity determination, a transcriptomic analysis was performed to test the effect of crambescidin-816 on the liver-derived tumor cells HepG2. Based on the results, we analyzed the effect of crambescidin-816 on cell-cell adhesion, cell-matrix adhesion, and cell migration by western blot, confocal microscopy, flow cytometry and transmission electron microscopy. Cytotoxicity and cell migration was also studied in several human tumor derived cell lines.
KEY RESULTS:
We show that crambescidin-816 is cytotoxic for all the cell lines studied. The compound inhibits cell-cell adhesion, interfering with the formation of tight junctions, and cell-matrix adhesion, negatively affecting focal adhesions. Finally crambescidin-816 inhibits cell migration as a consequence of the previously mentioned effects and also through the alteration of cytoskeleton dynamics.
CONCLUSIONS AND IMPLICATIONS:
The results indicate that crambescidin-816 is active against tumor cells and add new mechanism to the anti-tumor effect of this compound.