Biological characterization of the antiproliferative potential of Co(II) and Sn(IV) coordination compounds in human cancer cell lines: acomparative proteomic approach

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Abstract

Background : The discovery of cisplatin ' s antitumor activityled to a great interest in the potential application ofcoordination compounds as chemotherapeutic agents. Itis essential to identify new compounds that selectivelyinhibit tumor proliferation, evading secondary effects andresistance associated with chemotherapeutics.Methods: The in vitro antiproliferative potential of anorganotin(IV) compound was evaluated using colorectaland hepatocellular carcinoma, mammary gland adenocarcinomacell lines, and human fibroblasts. Tumor celldeath was evaluated by fluorescence microscopy andflow cytometry for the Sn(IV) compound and also for aCo(II) compound bearing 1,10-phenanthroline-5,6-dioneas ligand. Comparative proteomic analysis for both compoundswas assessed in the colorectal cancer cell line.Results: The Sn(IV) compound presented a high cytotoxiceffect in colorectal and hepatocellular carcinoma cell lines(IC 50 of 0.238 ± 0.011 μ M, 0.199 ± 0.003 μ M, respectively),and a lower cytotoxicity in human fibroblasts. Both compoundsinduced cell apoptosis and promoted the overexpressionof oxidative stress-related enzyme superoxidedismutase [Cu-Zn] (SODC). The Co(II) compound induceda decreased expression of anti-apoptotic proteins (translationally-controlled tumor protein and endoplasmin), andthe Sn(IV) compound decreased expression of proteinsinvolved in microtubule stabilization, TCTP, and cofilin-1.Conclusions: Our data reveals a high in vitro antiproliferativepotential against cancer cell lines and a moderateselectivity promoted by the Sn(IV) compound. Proteomic analysis of Sn(IV) and Co(II) compounds in the colorectalcancer cell line allowed an insight to their mechanismsof action, particularly by affecting the expression of proteinstypically deregulated in cancer, and also suggestinga promising therapeutic potential for both compounds.
Original languageUnknown
Pages (from-to)167-176
JournalDrug Metabolism And Drug Interactions
Volume28
Issue number3
DOIs
Publication statusPublished - 1 Jan 2013

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