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Mechanism of cytotoxic action of crambescidin‐816 on human liver‐derived tumour cells
Author(s) -
Rubiolo J A,
LópezAlonso H,
Roel M,
Vieytes M R,
Thomas O,
Ter E,
Vega F V,
Botana L M
Publication year - 2014
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.12552
Subject(s) - cytotoxic t cell , cytotoxicity , cell adhesion , cell adhesion molecule , cell , cell culture , microbiology and biotechnology , biology , flow cytometry , extracellular matrix , cell migration , chemistry , biochemistry , in vitro , genetics
Background and Purpose Marine sponges have evolved the capacity to produce a series of very efficient chemicals to combat viruses, bacteria, and eukaryotic organisms. It has been demonstrated that several of these compounds have anti‐neoplastic activity. The highly toxic sponge C rambe 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 analysed its effect on the 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 tumour cell HepG2 . Based on the results obtained, we analysed the effect of crambescidin‐816 on cell‐cell adhesion, cell‐matrix adhesion, and cell migration by W estern blot, confocal microscopy, flow cytometry and transmission electron microscopy. Cytotoxicity and cell migration were also studied in a variety of other cell lines derived from human tumours. Key Results Crambescidin‐816 had a cytotoxic effect on all the cell lines studied. It inhibited cell‐cell adhesion, interfered with the formation of tight junctions, and cell‐matrix adhesion, negatively affecting focal adhesions. It also altered the cytoskeleton dynamics. As a consequence of all these effects on cells crambescidin‐816 inhibited cell migration. Conclusions and Implications The results indicate that crambescidin‐816 is active against tumour cells and implicate a new mechanism for the anti‐tumour effect of this compound.