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- W2016774928 abstract "Few studies have examined the effects of polyamines on the action of DNA-binding anticancer drugs. Here, a Co(II)-mediated dimeric mithramycin (Mith) complex, (Mith)2−Co(II), was shown to be resistant to polyamine competition toward the divalent metal ion when compared to the Fe(II)-mediated drug complexes. Surface plasmon resonance experiments demonstrated that polyamines interfered with the binding capacity and association rates of (Mith)2−Co(II) binding to DNA duplexes, while the dissociation rates were not affected. Although (Mith)2−Co(II) exhibited the highest oxidative activity under physiological conditions (pH 7.3 and 37 °C), polyamines (spermine in particular) inhibited the DNA cleavage activity of the (Mith)2−Co(II) in a concentration-dependent manner. Depletion of intracellular polyamines by methylglyoxal bis(guanylhydrazone) (MGBG) enhanced the sensitivity of A549 lung cancer cells to (Mith)2−Co(II), most likely due to the decreased intracellular effect of polyamines on the action of (Mith)2−Co(II). Our study suggests a novel method for enhancing the anticancer activity of DNA-binding metalloantibiotics through polyamine depletion." @default.
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- W2016774928 date "2009-05-14" @default.
- W2016774928 modified "2023-09-27" @default.
- W2016774928 title "Effects of Polyamines on the DNA-Reactive Properties of Dimeric Mithramycin Complexed with Cobalt(II): Implications for Anticancer Therapy" @default.
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- W2016774928 doi "https://doi.org/10.1021/bi900092w" @default.
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