Mechanism of cytotoxic action of crambescidin-816 on human liver-derived tumour cells
| Type | : | ACL |
|---|---|---|
| Nature | : | Production scientifique |
| Au bénéfice du Laboratoire | : | Non |
| Statut de publication | : | Publié |
| Année de publication | : | 2014 |
| Auteurs (8) | : | RUBIOLO J,a LÓPEZ-ALONSO H ROEL M VIEYTES M,r THOMAS Olivier,p TERNON Eva VEGA F,v BOTANA L,m |
| Revue scientifique | : | British Journal of Pharmacology |
| Volume | : | 171 |
| Fascicule | : | 7 |
| Pages | : | 1655-1667 |
| DOI | : | 10.1111/bph.12552 |
| URL | : | https://doi.org/10.1111/bph.12552 |
| Abstract | : | 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 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 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 Western 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. |
| Mots-clés | : | crambescidin-816; transcriptomic analysis; tumour cell adhesion; tumour cell migration; tumour cell viability |
| Commentaire | : | - |
| Tags | : | - |
| Fichier attaché | : | - |
| Citation | : |
Rubiolo JA, López-Alonso H, Roel M, Vieytes MR, Thomas OP, Ternon E, Vega FV, Botana LM (2014) Mechanism of cytotoxic action of crambescidin-816 on human liver-derived tumour cells. Br J Pharmacol 171: 1655-1667 | doi: 10.1111/bph.12552
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