ecteinascidin-770 and Lung-Neoplasms

The strategies for achieving anti-metastasis have received increased research interest and clinical attention. The anoikis-sensitizing effect of ecteinascidin 770 (ET-770) was investigated in the present study in non-small cell lung cancer cells.. ET-770 isolated from Ecteinascidia thurstoni was tested for its anoikis-sensitizing effect on H23 and H460 human lung cancer cells by 2,3-b-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide salt (XTT) assay. The levels of proteins being involved in anoikis of cells were determined by western blot analysis.. ET-770 was shown to enhance anoikis response of human lung cancer H23 cells in a dose-dependent manner. The underlying mechanism was investigated and it was found that ET-770 sensitized the cells by activating the p53 protein, which in turn down-regulated anti-apoptotic myeloid cell leukemia sequence-1 (MCL1) and up-regulated BCL2-associated X protein (BAX) proteins. However, B-cell lymphoma-2 (BCL2) proteins were not significantly affected by ET-770. Further, the anoikis sensitization of ET-770 was observed in H460 lung cancer cells.. The present results reveal for the first time that ET-770 can sensitize anoikis through the p53 pathway and further development of this compound for therapeutic use is warranted.

Topics: Anoikis; Antineoplastic Agents; Blotting, Western; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Heterocyclic Compounds, 4 or More Rings; Humans; Isoquinolines; Lung Neoplasms; Signal Transduction