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Issue 12, 2013
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The hexacarbonyldicobalt derivative of aspirin acts as a CO-releasing NSAID on malignant mesothelioma cells

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Abstract

The antiproliferative activity of the aspirin derivative [2-acetoxy-(2-propynyl)benzoate]hexacarbonyldicobalt (Co-ASS) and its analogue hexacarbonyl[μ-(2-ethylphenyl)methanol]dicobalt (Co-EPM) was investigated on malignant pleural mesothelioma (MPM) cell lines, having an epithelioid or a sarcomatoid phenotype. In sarcomatoid cell lines Co-ASS was more potent than Co-EPM and the prototypal metallo-drug cisplatin, and induced cell death through the intrinsic apoptotic pathway, associated with a strong NF-κB inhibition. In contrast, both Co-ASS and Co-EPM showed only a modest cytostatic activity against epithelioid MPM cells. Co-EPM induced an increase of senescent cells, while Co-ASS did not; the different outcomes were traced back to the organic (aspirin-like) portion of the molecule. Both Co-EPM and Co-ASS significantly reduced reactive oxygen/nitrogen species (ROS/RNS), and in turn nitrites, suggesting that the hexacarbonyldicobalt moiety may deliver CO within the cell, acting as a CO-releasing molecule (CO-RM). In perspective, Co-ASS would be better considered as a CO-NSAID agent (a CO-releasing molecule retaining the NSAID properties similar to NO- and H2S-NSAIDs) than as an antitumor drug candidate.

Graphical abstract: The hexacarbonyldicobalt derivative of aspirin acts as a CO-releasing NSAID on malignant mesothelioma cells

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Publication details

The article was received on 10 Apr 2013, accepted on 16 Aug 2013 and first published on 19 Aug 2013


Article type: Paper
DOI: 10.1039/C3MT00117B
Citation: Metallomics, 2013,5, 1604-1613
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    The hexacarbonyldicobalt derivative of aspirin acts as a CO-releasing NSAID on malignant mesothelioma cells

    I. Zanellato, I. Bonarrigo, M. Ravera, E. Gabano, R. Gust and D. Osella, Metallomics, 2013, 5, 1604
    DOI: 10.1039/C3MT00117B

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