NDLI: A dual-targeting, apoptosis-inducing organometallic half-sandwich iridium anticancer complex

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Metallomics Vol - 6 Issue - 7

Metallomics Vol - 6 Issue - 6

Metallomics Vol - 6 Issue - 5

Metallomics Vol - 6 Issue - 4

Metallomics Vol - 6 Issue - 3

Metallomics Vol - 6 Issue - 2

A dual-targeting, apoptosis-inducing organometallic half-sandwich iridium anticancer complex

Content Provider	Royal Society of Chemistry (RSC)
Author	Liu, Zhe Sadler, Peter J. Zerzankova, Lenka Kisova, Anna Stepankova, Jana Kasparkova, Jana Brabec, Viktor Novohradsky, Vojtech Kostrhunova, Hana
Copyright Year	2014
Abstract	The cellular mechanism of action of an iridium(III) half-sandwich complex [(η5-C5Me4C6H4C6H5)Ir(phen)Cl]PF6 (phen = phenanthroline) (1) is reported. Complex 1 was used to treat several cell lines, including cisplatin-sensitive, cisplatin-resistant (with intrinsic and acquired resistance) carcinoma cells with wild type p53 status as well as the cells with no intact p53 gene, and nontumorigenic cells. Complex 1 preferentially kills cancer cells over nontumorigenic cells and exhibits no cross-resistance with cisplatin. It appears to retain significant activity in human tumor cell lines that are refractory or poorly responsive to cisplatin, and in contrast to cisplatin it displays a high activity in human tumor cell lines that are characterized by both wild type and mutant p53 gene. The mechanism of cell killing was established through detailed cell-based assays. Complex 1 exhibits dual effects in killing cancer cells causing nuclear DNA damage and mitochondrial dysfunction involving ROS production simultaneously. Flow cytometric studies and impedance-based monitoring of cellular responses to 1 demonstrated that 1 acts more quickly than cisplatin to induce cell death and that 1 is a more effective apoptosis inducer than cisplatin in particular in early stages of treatment, when the apoptotic effects predominate over necrosis. Overall, our findings confirm that 1 and its iridium derivatives represent promising candidates for further pre-clinical studies and new additions to the growing family of nonplatinum metal-based anticancer complexes.
Starting Page	1491
Ending Page	1501
Page Count	11
File Format	HTM / HTML PDF
ISSN	17565901
Volume Number	6
Issue Number	8
Journal	Metallomics
DOI	10.1039/c4mt00112e
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	Flow cytometry Reactive oxygen species Carcinoma Cisplatin P53 Necrosis Gene DNA Iridium Phenanthroline Mutation Cancer Apoptosis
Content Type	Text
Resource Type	Article
Subject	Chemistry Medicine Metals and Alloys Biochemistry Biomaterials Biophysics

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