• Br J Anaesth · Aug 2012

    Lidocaine time- and dose-dependently demethylates deoxyribonucleic acid in breast cancer cell lines in vitro.

    • P Lirk, R Berger, M W Hollmann, and H Fiegl.
    • Department of Anaesthesiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105AZ Amsterdam, The Netherlands. p.lirk@amc.uva.nl
    • Br J Anaesth. 2012 Aug 1; 109 (2): 200-7.

    BackgroundAnaesthetic management of cancer surgery may influence tumour recurrence. The modulation of gene expression by methylation of deoxyribonucleic acid (DNA) (epigenetics) is increasingly recognized as a major hallmark of cancer. Next to direct effects of local anaesthetics upon tumour cells, the ester-type local anaesthetic, procaine, has been shown to affect methylation status in several tumour cell lines, promoting the reactivation of tumour suppressor genes. We sought to determine whether the prototype amide-type local anaesthetic, lidocaine, influences the survival and epigenetic status of oestrogen receptor (ER)-positive and -negative breast cancer cell lines in vitro.MethodsBreast cancer cell lines BT-20 (ER-negative) and MCF-7 (ER-positive) were incubated with lidocaine and procaine as the reference substance. We performed cell count and determined apoptosis using TUNEL stain. Further, we assessed global methylation status, and methylation of three known tumour suppressor genes (RASSF1A, MYOD1, and GSTP1) using the MethyLight assay and real-time quantitative polymerase chain reaction, respectively.ResultsBaseline methylation was 100-fold higher in BT-20 cells. Here, we observed a dose-dependent decrease in DNA methylation in response to lidocaine (1, 0.01, and 0.01 mM) after 72 h (P<0.001, <0.001, and 0.004, respectively). The corresponding changes were smaller in MCF-7 cells. Global methylation status was profoundly influenced, but the methylation and mRNA expression status of three tumour suppressor genes was unchanged.ConclusionsOur findings suggest that demethylating tumour-suppressive effects of anaesthetic interventions may only be detectable in specific types of cancer due to differential methylation profiles. In conclusion, at clinically relevant concentrations, lidocaine demethylates DNA of breast cancer cell lines in vitro.

      Pubmed     Free full text   Copy Citation     Plaintext  

      Add institutional full text...

    Notes

     
    Knowledge, pearl, summary or comment to share?
    300 characters remaining
    help        
    You can also include formatting, links, images and footnotes in your notes
    • Simple formatting can be added to notes, such as *italics*, _underline_ or **bold**.
    • Superscript can be denoted by <sup>text</sup> and subscript <sub>text</sub>.
    • Numbered or bulleted lists can be created using either numbered lines 1. 2. 3., hyphens - or asterisks *.
    • Links can be included with: [my link to pubmed](http://pubmed.com)
    • Images can be included with: ![alt text](https://bestmedicaljournal.com/study_graph.jpg "Image Title Text")
    • For footnotes use [^1](This is a footnote.) inline.
    • Or use an inline reference [^1] to refer to a longer footnote elseweher in the document [^1]: This is a long footnote..

    hide…