Distinct cellular fates for KP1019 and NAMI-A determined by X-ray fluorescence imaging of single cells

被引：86

作者：

Aitken, Jade B. ^{[2
,3
,4
]}

Antony, Sumy ^{[1
,5
]}

Weekley, Claire M. ^{[1
]}

Lai, Barry ^{[6
]}

Spiccia, Leone ^{[5
]}

Harris, Hugh H. ^{[1
]}

机构：

[1] Univ Adelaide, Sch Chem & Phys, Adelaide, SA 5005, Australia

[2] Univ Sydney, Sch Chem, Sydney, NSW 2006, Australia

[3] Australian Synchrotron, Clayton, Vic 3168, Australia

[4] KEK, Inst Mat Struct Sci, Tsukuba, Ibaraki 3050801, Japan

[5] Monash Univ, Sch Chem, Clayton, Vic 3800, Australia

[6] Argonne Natl Lab, Xray Sci Div, Argonne, IL 60439 USA

来源：

METALLOMICS | 2012年 / 4卷 / 10期

基金：

澳大利亚研究理事会;

关键词：

RUTHENIUM COMPLEXES; ANTICANCER DRUGS; SERUM-ALBUMIN; PHASE-I; TUMOR; BINDING; METASTASIS; INHIBITION; ABSORPTION; INDAZOLIUM;

D O I：

10.1039/c2mt20072d

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Small molecule ruthenium complexes show great promise as anticancer pharmaceuticals, but further rational development of these as drugs is stymied by an incomplete understanding of the mechanisms that give rise to markedly different biological behaviour for structurally similar species. X-ray fluorescence imaging at two incident energies was used to reveal the intracellular distribution of Ru in single human cells treated with KP1019, showing Ru localised in both cytosol and in the nuclear region. In addition the imaging showed that treatment with KP1019 modulated Fe distribution to resemble the Ru distribution, without affecting cellular Fe content. In stark contrast, Ru could not be visualised in cells treated with NAMI-A, indicating that it was not internalised and supporting the proposition that its activity is exerted through a membrane-binding mechanism.

引用

页码：1051 / 1056

页数：6

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