Proapoptotic activity in vitro of two novel ruthenium(II) complexes with flavanone-based ligands that overcome cisplatin resistance in human bladder carcinoma cells |
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Authors: | Kasprzak Maria M Szmigiero Leszek Zyner Elżbieta Ochocki Justyn |
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Affiliation: | a Department of Bioinorganic Chemistry, Medical University, Muszynskiego 1, 90-151 Lodz, Polandb Department of Nucleic Acids Biochemistry, Medical University, Mazowiecka 6/8, 92-215 Lodz, Poland |
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Abstract: | In this study we examined their proapoptotic activity of cis-dichloridobis(3-imino-2-methoxyflavanone)ruthenium(II)3H2O (1) and cis-dichloridobis(3-imino-2-ethoxyflavanone)ruthenium(II)2H2O (2) towards human bladder carcinoma cell line EJ and its cisplatin resistant subline EJcisR. On the basis of the experiments we carried out, it may be concluded, that: CDDP (cis-diamminedichloridoplatinum) resistance of EJcisR cells is probably based on partial loss of apoptotic pathway activating caspase-8 and increased resistance to DNA strand breaks and/or alkali-labile sites. Increased glutathione levels, as well as activity of P-gp transporter seems to be not relevant in this case. The proapoptotic activity of the ruthenium compounds is higher than that of cisplatin. Higher proapoptotic activity of 1 and 2 when compared to CDDP may be due to the presence of large, lipophilic flavanone-based ligands that may facilitate their trans-membrane transport and their redox activity. 1 and 2 induce apoptosis apparently in more than one way. Although caspase-8 activation and DNA strand breaks and/or alkali-labile sites are caused by the compounds, their ability to cause the oxidative stress in the cells may also participate in apoptosis induction. |
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Keywords: | Ruthenium(II) complexes Flavonoids Apoptosis Cisplatin-resistance |
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