Antiproliferative effect of ferrocifen drug candidates on malignant pleural mesothelioma cell lines |
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Authors: | Ilaria Zanellato Anne Vessières Domenico Osella |
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Institution: | a Dipartimento di Scienze dell’Ambiente e della Vita, Università del Piemonte Orientale “Amedeo Avogadro”, Via T. Michel 11, 15100 Alessandria, Italy b Laboratoire de Chimie et Biochimie des Complexes Moléculaires, UMR CNRS 7576, Ecole Nationale Supérieure de Chimie de Paris, 11, rue Pierre et Marie Curie, 75231 Paris 05, France |
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Abstract: | The purpose of this study was to investigate the antiproliferative potential of two novel bio-organometallic drug candidates, based on hydroxyl-phenyl-but-1-ene skeleton and containing the ferrocenyl (Fc) moiety, namely ferrociphenol (Fc-diOH) and ferrocifen (Fc-OH-TAM), on two cell lines, named BR95 (epithelial-like) and MM98 (sarcomatous-like), obtained from pleural effusions of previously untreated malignant pleural mesothelioma (MPM) patients. In vitro chemosensitivity of MPM cells towards the title compounds was evaluated by cell viability assay, alkaline Single Cell Gel Electrophoresis (Comet test) and western blotting evaluation of p53 induction. The two bio-organometallic derivatives were found to be more potent in inhibiting cell proliferation than the reference metallo-drug cisplatin (CDDP). This antiproliferative effect cannot be attributed to estrogenic/antiestrogenic activity, since both cell lines resulted to be estrogen insensitive (ER−). Fc-diOH and CDDP were able to upregulate wild type p53 present in MM98 cell line, while Fc-OH-TAM was not. Similarly, Fc-diOH and CDDP induced early DNA damage, while Fc-OH-TAM did not. This indicates that, albeit the similar structures, the two ferrocifens exhert different mechanisms of cytotoxicity on MPM cells. |
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Keywords: | cisplatin or CDDP cis-diamminedichloroplatinum (II) Comet assay single cell gel electrophoresis CT continuous treatment E2 estrogen ER&minus estrogen insensitive ER estrogen receptor ER+ estrogen sensitive Fc-diOH (1 1-bis(4-hydroxy-phenyl)-2-ferrocenyl-but-1-ene: ferrociphenol Fc-OH-TAM 1-[4-(-O(CH2)3NMe2)phenyl]-1-(4-hydroxy-phenyl)-2-ferrocenyl-but-1-ene): ferrocifen HRP horse radish peroxidase MM malignant mesothelioma MPM malignant pleural mesothelioma MTS (3-(4 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) PBS phosphate buffered saline R recovery TAM tamoxifen |
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