Bohic, Sylvain

Cloetens, Peter

Hands-Portman, Ian J.

Romero-canelón, Isolda

Sadler, Peter J.

Sanchez-cano, Carlos

Yang, Yang

English

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

University of Birmingham Research Portal

Synchrotron X-Ray Fluorescence Nanoprobe Reveals Target Sites for Organo-Osmium Complex in Human Ovarian Cancer Cells

http://pure-oai.bham.ac.uk/ws/files/48553439/Sanchez_Cano_et_al_2017_Chemistry_A_European_Journal.pdf

Synchrotron X-Ray Fluorescence Nanoprobe Reveals Target Sites for Organo-Osmium Complex in Human Ovarian Cancer Cells

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University of Birmingham Research Portal

University of Birmingham Research Portal