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.
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 tumour models and the possibility of changing the non-arene ligands to tune the anticancer activity of osmium in vivo.
Bergamo
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A
Callerio Foundation Onlus, Via A. Fleming 22-31, 34127 Trieste, Italy. a.bergamo@callerio.org
Masi
A
A
Peacock
A F A
AF
Habtemariam
A
A
Sadler
P J
PJ
Sava
G
G
D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002277:Carcinoma / Q000188:drug therapy* / Q000556:secondary; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D020782:Matrix Metalloproteinases / Q000187:drug effects; D051379:Mice; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009942:Organometallic Compounds / Q000737:chemistry / Q000627:therapeutic use*; D009992:Osmium / Q000737:chemistry / Q000627:therapeutic use*; D012428:Ruthenium / Q000737:chemistry / Q000627:therapeutic use*
D009942:Organometallic Compounds; C501327:RM175; D009992:Osmium; D012428:Ruthenium; D020782:Matrix Metalloproteinases