کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1317045 | 976502 | 2011 | 7 صفحه PDF | دانلود رایگان |
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.
Graphical AbstractTwo novel ruthenium compounds with flavanone-based ligands induce apoptosis in bladder cancer cells both sensitive and resistant to cisplatin.Figure optionsDownload as PowerPoint slide
Journal: Journal of Inorganic Biochemistry - Volume 105, Issue 4, April 2011, Pages 518–524