Cytotoxic (salen)ruthenium(iii) anticancer complexes exhibit different modes of cell death directed by axial ligands. Issue 10 (16th August 2017)

• Record Type: Journal Article
• Authors: Li, Cai; Ip, Kwok-Wa; Man, Wai-Lun; Song, Dan; He, Ming-Liang; Yiu, Shek-Man; Lau, Tai-Chu; Zhu, Guangyu
• Is Part Of: Chemical science. Volume 8:Issue 10(2017)
• Page Start: 6865
• Page End: 6870
• Publication Date: 2017-08-16
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c7sc02205k
• Languages: English
• ISSNs: 2041-6520

Abstract

Abstract : A cancer-cell selective bis(guanidine)-ruthenium(iii ) complex induces apoptosis, whereas its amidine analogue effectively kills cancer cells through paraptosis pathways. 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 complex7 and the amidine complex13 reveals two distinguished modes of action. Complex7 weakly binds to DNA and induces DNA damage, cell cycle arrest, and typical apoptosis pathways in MCF-7 cells. In contrast, complex13 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.