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In vivo tumour and metastasis reduction and in vitro effects on invasion assays of the ruthenium RM175 and osmium AFAP51 organometallics in the mammary cancer model

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Bergamo, A., Masi, A., Peacock, Anna F. A., Habtemariam, Abraha, Sadler, P. J. and Sava, G.. (2010) In vivo tumour and metastasis reduction and in vitro effects on invasion assays of the ruthenium RM175 and osmium AFAP51 organometallics in the mammary cancer model. Journal of Inorganic Biochemistry, Vol.104 (No.1). pp. 79-86. ISSN 0162-0134

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Abstract

We have compared the organometallic arene complexes [(eta(6)-biphenyl)M(ethylenediamine)Cl](+) RM175 (M = Ru-II) and its isostructural osmium(II) analogue AFAP51 (M = Os-II) for their ability to induce cell detachment resistance from fibronectin, collagen IV and poly-L-lysine, and cell re-adhesion after treatment, their effects on cell migration and cell viability, on matrix metalloproteinases production, and on primary tumour growth of MCa mammary carcinoma, the effect of human serum albumin on their cytotoxicity. There are differences between ruthenium and osmium. The Os complex is up to 6x more potent than RM175 towards highly-invasive breast MDA-MB-231, human breast MCF-7 and human epithelial HBL-100 cancer cells, but whereas RM175 was active against MCa mammary carcinoma in vivo and caused metastasis reduction, AFAP51 was not. Intriguingly the presence of human serum albumin in the growth medium enhanced the cytotoxicity of both compounds. RM175 increased the resistance of MDA-MB-231 cells to detachment from substrates and both compounds inhibited the production of MMP-2. These data confirm the key role of ruthenium itself in anti-metastatic activity. It will be interesting to explore the activity of osmium arene complexes in other turnout models and the possibility of changing the non-arene ligands to tune the anticancer activity of osmium in vivo. (C) 2009 Elsevier Inc. All rights reserved.

Item Type: Journal Article
Subjects: Q Science > QD Chemistry
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
R Medicine > RM Therapeutics. Pharmacology
Divisions: Faculty of Science > Chemistry
Library of Congress Subject Headings (LCSH): Metastasis, Mammary glands -- Cancer, Ruthenium compounds -- Therapeutic use, Osmium compounds -- Therapeutic use, Organometallic compounds -- Therapeutic use
Journal or Publication Title: Journal of Inorganic Biochemistry
Publisher: Elsevier Science Inc
ISSN: 0162-0134
Date: January 2010
Volume: Vol.104
Number: No.1
Number of Pages: 8
Page Range: pp. 79-86
Identification Number: 10.1016/j.jinorgbio.2009.10.005
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Restricted or Subscription Access
Funder: Fondazione CRTrieste, Friuli-Venezia Giulia (Italy)
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URI: http://wrap.warwick.ac.uk/id/eprint/16839

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