کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2580454 | 1561622 | 2014 | 10 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: The activity of a novel mithramycin analog is related to its binding to DNA, cellular accumulation, and inhibition of Sp1-driven gene transcription The activity of a novel mithramycin analog is related to its binding to DNA, cellular accumulation, and inhibition of Sp1-driven gene transcription](/preview/png/2580454.png)
• The binding of DIG-MSK, an analog of mithramycin A, to DNA is examined.
• The effects of DIG-MSK on Sp1- and Sp3-driven gene transcription are analyzed.
• DIG-MSK shares “anti-transcriptional” properties with other mithramycin analogs.
• DIG-MSK alters the transcription of endogenous genes in ovarian cancer cells.
DIG-MSK (demycarosyl-3D-β-d-digitoxosyl-mithramycin SK) is a recently isolated compound of the mithramycin family of antitumor antibiotics, which includes mithramycin A (MTA) and mithramycin SK (MSK). Here, we present evidence that the binding of DIG-MSK to DNA shares the general features of other mithramycins such as the preference for C/G-rich tracts, but there are some differences in the strength of binding and the DNA sequence preferentially recognized by DIG-MSK. We aimed at gaining further insights into the DIG-MSK mechanism of action by direct comparison with the effects of the parental MTA. Similar to MTA, MSK and DIG-MSK accumulated rapidly in A2780, IGROV1 and OVCAR3 human ovarian cancer cell lines, and DIG-MSK was a potent inhibitor of both basal and induced expression of an Sp1-driven luciferase vector. This inhibitory activity was confirmed for the endogenous Sp1 gene and a set of Sp-responsive genes, and compared to that of MTA and MSK. Furthermore, DIG-MSK was stronger than MTA as inhibitor of Sp3-driven transcription and endogenous Sp3 gene expression. Differences in the effects of MTA, MSK and DIG-MSK on gene expression may have a large influence on their biological activities.
Journal: Chemico-Biological Interactions - Volume 219, 5 August 2014, Pages 123–132