An Organoruthenium Anticancer Agent Shows Unexpected Target Selectivity For Plectin

被引：99

作者：

Meier, Samuel M. ^{[1
,2
,3
]}

Kreutz, Dominique ^{[1
]}

Winter, Lilli ^{[4
]}

Klose, Matthias H. M. ^{[2
,3
,5
]}

Cseh, Klaudia ^{[5
]}

Weiss, Tamara ^{[6
]}

Bileck, Andrea ^{[1
]}

Alte, Beatrix ^{[7
]}

Mader, Johanna C. ^{[1
]}

Jana, Samir ^{[8
]}

Chatterjee, Annesha ^{[8
]}

Bhattacharyya, Arindam ^{[8
]}

Hejl, Michaela ^{[5
]}

Jakupec, Michael A. ^{[2
,3
,5
]}

Heffeter, Petra ^{[2
,3
,7
]}

Berger, Walter ^{[2
,3
,7
]}

Hartinger, Christian G. ^{[9
]}

Keppler, Bernhard K. ^{[2
,3
,5
]}

Wiche, Gerhard ^{[4
]}

Gerner, Christopher ^{[1
]}

机构：

[1] Univ Vienna, Inst Analyt Chem, Wahringer Str 38, A-1090 Vienna, Austria

[2] Univ Vienna, Forschungsplattform Translat Canc Therapy Res, Vienna, Austria

[3] Med Univ Wien, Vienna, Austria

[4] Univ Vienna, Dept Biochem & Cell Biol MFPL, Dr Bohr Gasse 9, A-1030 Vienna, Austria

[5] Univ Vienna, Inst Anorgan Chem, Vienna, Austria

[6] St Anna Kinderkrebsforsch, Vienna, Austria

[7] Med Univ Wien, Inst Krebsforsch, Vienna, Austria

[8] Univ Calcutta, Dept Zool, 35 Ballygunge Circular Rd, Kolkata, W Bengal, India

[9] Univ Auckland, Sch Chem Sci, Auckland, New Zealand

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2017年 / 56卷 / 28期

关键词：

anticancer agents; plectin; proteomics; ruthenium; target identification; INTERMEDIATE-FILAMENT; PROTEIN; CELLS; IDENTIFICATION; RUTHENIUM;

D O I：

10.1002/anie.201702242

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Organometallic metal(arene) anticancer agents require ligand exchange for their anticancer activity and this is generally believed to confer low selectivity for potential cellular targets. However, using an integrated proteomics-based target-response profiling approach as a potent hypothesis-generating procedure, we found an unexpected target selectivity of a ruthenium(arene) pyridinecarbothioamide (plecstatin) for plectin, a scaffold protein and cytolinker, which was validated in a plectin knock-out model in vitro. Plectin targeting shows potential as a strategy to inhibit tumor invasiveness as shown in cultured tumor spheroids while oral administration of plec-statin-1 to mice reduces tumor growth more efficiently in the invasive B16 melanoma than in the CT26 colon tumor model.

引用

页码：8267 / 8271

页数：5

共 27 条

[1] Ligand substitutions between ruthenium-cymene compounds can control protein versus DNA targeting and anticancer activity [J].