Cytotoxic (salen)ruthenium(III) anticancer complexes exhibit different modes of cell death directed by axial ligands. Li, C., Ip, K. W., Man, W. L., Song, D., He, M. L., Yiu, S. M., Lau, T. C., & Zhu, G. Chemical Science, 8(10):6865–6870, 2017. Publisher: Royal Society of Chemistrydoi abstract bibtex Two novel series of (salen)ruthenium(iii) complexes bearing guanidine and amidine axial ligands were synthesized, characterized, and evaluated for anticancer activity. In vitro cytotoxicity tests demonstrate that these complexes are cytotoxic against various cancer cell lines and the leading complexes have remarkable cancer-cell selectivity. A detailed study of the guanidine complex 7 and the amidine complex 13 reveals two distinguished modes of action. Complex 7 weakly binds to DNA and induces DNA damage, cell cycle arrest, and typical apoptosis pathways in MCF-7 cells. In contrast, complex 13 induces paraptosis-like cell death hallmarked by massive vacuole formation, mitochondrial swelling, and ER stress, resulting in significant cytotoxicity against human breast cancer cells. Our results provide an extraordinary example of tuning the mechanism of action of (salen)ruthenium(iii) anticancer complexes by modifying the structure of the axial ligands.
@article{li_cytotoxic_2017,
title = {Cytotoxic (salen)ruthenium({III}) anticancer complexes exhibit different modes of cell death directed by axial ligands},
volume = {8},
issn = {20416539},
doi = {10.1039/c7sc02205k},
abstract = {Two novel series of (salen)ruthenium(iii) complexes bearing guanidine and amidine axial ligands were synthesized, characterized, and evaluated for anticancer activity. In vitro cytotoxicity tests demonstrate that these complexes are cytotoxic against various cancer cell lines and the leading complexes have remarkable cancer-cell selectivity. A detailed study of the guanidine complex 7 and the amidine complex 13 reveals two distinguished modes of action. Complex 7 weakly binds to DNA and induces DNA damage, cell cycle arrest, and typical apoptosis pathways in MCF-7 cells. In contrast, complex 13 induces paraptosis-like cell death hallmarked by massive vacuole formation, mitochondrial swelling, and ER stress, resulting in significant cytotoxicity against human breast cancer cells. Our results provide an extraordinary example of tuning the mechanism of action of (salen)ruthenium(iii) anticancer complexes by modifying the structure of the axial ligands.},
number = {10},
journal = {Chemical Science},
author = {Li, Cai and Ip, Kwok Wa and Man, Wai Lun and Song, Dan and He, Ming Liang and Yiu, Shek Man and Lau, Tai Chu and Zhu, Guangyu},
year = {2017},
note = {Publisher: Royal Society of Chemistry},
pages = {6865--6870},
}
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