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- Title
Synchrotron X-Ray Fluorescence Nanoprobe Reveals Target Sites for Organo-Osmium Complex in Human Ovarian Cancer Cells.
- Authors
Sanchez‐Cano, Carlos; Romero‐Canelón, Isolda; Yang, Yang; Hands‐Portman, Ian J.; Bohic, Sylvain; Cloetens, Peter; Sadler, Peter J.
- Abstract
A variety of transition metal complexes exhibit anticancer activity, but their target sites in cells need to be identified and mechanisms of action elucidated. Here, it was found that the sub-cellular distribution of [Os(η6- p-cym)(Azpy-NMe2)I]+ ( p-cym= p-cymene, Azpy-NMe2=2-( p-[dimethylamino]phenylazo)pyridine) ( 1), a promising drug candidate, can be mapped in human ovarian cancer cells at pharmacological concentrations using a synchrotron X-ray fluorescence nanoprobe (SXRFN). SXRFN data for Os, Zn, Ca, and P, as well as TEM and ICP analysis of mitochondrial fractions suggest localization of Os in mitochondria and not in the nucleus, accompanied by mobilization of Ca from the endoplasmic reticulum, a signaling event for cell death. These data are consistent with the ability of 1 to induce rapid bursts of reactive oxygen species and especially superoxide formed in the first step of O2 reduction in mitochondria. Such metabolic targeting differs from the action of Pt drugs, offering promise for combatting Pt resistance, which is a current clinical problem.
- Subjects
TRANSITION metal compounds synthesis; OVARIAN cancer treatment; ANTINEOPLASTIC agent synthesis; OSMIUM compounds; PLATINUM; CANCER cells; DRUG resistance in cancer cells; X-ray fluorescence; THERAPEUTICS
- Publication
Chemistry - A European Journal, 2017, Vol 23, Issue 11, p2512
- ISSN
0947-6539
- Publication type
Article
- DOI
10.1002/chem.201605911