title: Lidocaine and ropivacaine, but not bupivacaine, demethylate deoxyribonucleic acid in breast cancer cells in vitro.
abstract: BACKGROUND
  Lidocaine demethylates deoxyribonucleic acid (DNA) in breast cancer cells. This modification of epigenetic information may be of therapeutic relevance in the perioperative period, because a decrease in methylation can reactivate tumour suppressor genes and inhibit tumour growth. The objectives of this study were to determine the effect of two amide local anaesthetics, ropivacaine and bupivacaine, on methylation in two breast cancer cell lines and to detect whether the combination of lidocaine with the chemotherapy agent 5-aza-2'-deoxycytidine (DAC) would result in additive demethylating effects.
  
  
  METHODS
  Breast cancer cell lines BT-20 [oestrogen receptor (ER)-negative] and MCF-7 (ER-positive) were incubated with lidocaine, bupivacaine, and ropivacaine to assess demethylating properties. Then, we tested varying concentrations of lidocaine and DAC to assess whether their demethylating effects were additive. Cell numbers and global methylation status were analysed.
  
  
  RESULTS
  Lidocaine decreased methylation in BT-20 and MCF-7 cells, ropivacaine decreased methylation in BT-20 cells, and bupivacaine had no demethylating effect. When combined, lidocaine and DAC had additive demethylating effects.
  
  
  CONCLUSIONS
  At clinically relevant doses, lidocaine and ropivacaine exert demethylating effects on specific breast cancer cell lines, but bupivacaine does not. The demethylating effects of lidocaine and DAC are indeed additive.
authors.affiliation: Department of Anaesthesiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Amsterdam 1105AZ, The Netherlands p.lirk@amc.uva.nl heidelinde.fiegl@i-med.ac.at.
authors.forename: P
authors.initials: P
authors.lastname: Lirk
authors.affiliation: Department of Anaesthesiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Amsterdam 1105AZ, The Netherlands.
authors.forename: M W
authors.initials: MW
authors.lastname: Hollmann
authors.affiliation: Department of Gynaecology and Obstetrics, Innsbruck Medical University, Anichstr. 35, Innsbruck 6020, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Fleischer
authors.affiliation: Department of Anaesthesiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Amsterdam 1105AZ, The Netherlands.
authors.forename: N C
authors.initials: NC
authors.lastname: Weber
authors.affiliation: Department of Gynaecology and Obstetrics, Innsbruck Medical University, Anichstr. 35, Innsbruck 6020, Austria p.lirk@amc.uva.nl heidelinde.fiegl@i-med.ac.at.
authors.forename: H
authors.initials: H
authors.lastname: Fiegl
mesh_terms: D000577:Amides / Q000008:administration & dosage / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000494:pharmacology*; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology; D001374:Azacitidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002045:Bupivacaine / Q000008:administration & dosage / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D019175:DNA Methylation / Q000187:drug effects*; D004273:DNA, Neoplasm / Q000235:genetics; D000077209:Decitabine; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D044127:Epigenesis, Genetic / Q000187:drug effects; D005260:Female; D006801:Humans; D008012:Lidocaine / Q000008:administration & dosage / Q000494:pharmacology*; D061986:MCF-7 Cells; D000077212:Ropivacaine; D014407:Tumor Cells, Cultured
chemical_list: D000577:Amides; D000779:Anesthetics, Local; D000964:Antimetabolites, Antineoplastic; D004273:DNA, Neoplasm; D000077209:Decitabine; D000077212:Ropivacaine; D008012:Lidocaine; D001374:Azacitidine; D002045:Bupivacaine
keywords: cancer; demethylation; epigenetics; local anaesthetic, bupivacaine; local anaesthetic, lidocaine; local anaesthetic, ropivacaine