BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.
BACKGROUND: 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. MATERIALS AND METHODS:ET-770 isolated from Ecteinascidia thurstoni was tested for its anoikis-sensitizing effect on H23 and H460 humanlung 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. RESULTS:ET-770 was shown to enhance anoikis response of humanlung 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. CONCLUSION: 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.
Authors: Amira Hosni-Ahmed; Michelle Sims; Terreia S Jones; Renukadevi Patil; Shivaputra Patil; Hossam Abdelsamed; Charles R Yates; Duane D Miller; Lawrence M Pfeffer Journal: J Cancer Sci Ther Date: 2014-09-25