title: Local anesthetics induce apoptosis in human breast tumor cells.
abstract: BACKGROUND
  Previous studies have shown that local anesthetics may induce apoptosis in some cell types. In this study, we investigated the apoptotic effects of local anesthetics in human breast tumor cells.
  
  
  METHODS
  Human breast cancer (MCF-7) and mammary epithelial (MCF-10A) cell lines were treated with lidocaine and/or bupivacaine. Cell viability, DNA fragmentation, and annexin V immunofluorescence staining were assessed. The effects on apoptosis-related protein expression were investigated by Western blot analysis. The findings were extended to studies in an in vivo xenograft model.
  
  
  RESULTS
  Treatment of breast tumor cells with lidocaine and bupivacaine resulted in inhibition of cell viability via induction of apoptosis. The effects were more prominent in MCF-7 cells than in MCF-10A cells. Treatment with local anesthetics induced caspase 7, 8, 9, and poly ADP-ribose polymerase cleavage. The cleavage of caspase 7 and poly ADP-ribose polymerase induced by local anesthetics were effectively blocked by caspase inhibitors. Furthermore, treatment of MCF-7 xenografts with local anesthetics resulted in higher expression of cleaved caspase 7 and an increase in terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining.
  
  
  CONCLUSIONS
  Lidocaine and bupivacaine induce apoptosis of breast tumor cells at clinically relevant concentrations. Our results reveal previously unrecognized beneficial actions of local anesthetics and call for further studies to assess the oncologic advantages of their use during breast cancer surgery.
authors.affiliation: From the *Graduate Institute of Physiology, National Taiwan University College of Medicine; †Department of Surgery, Mackay Memorial Hospital; ‡Mackay Junior College of Medicine, Nursing, and Management, Taipei; §Mackay Medical College, New Taipei City; and Departments of ‖Anesthesiology, and ¶Medical Research, Mackay Memorial Hospital, Taipei, Taiwan.
authors.forename: Yuan-Ching
authors.initials: YC
authors.lastname: Chang
authors.forename: Chien-Liang
authors.initials: CL
authors.lastname: Liu
authors.forename: Ming-Jen
authors.initials: MJ
authors.lastname: Chen
authors.forename: Yung-Wei
authors.initials: YW
authors.lastname: Hsu
authors.forename: Shan-Na
authors.initials: SN
authors.lastname: Chen
authors.forename: Chi-Hsin
authors.initials: CH
authors.lastname: Lin
authors.forename: Chin-Man
authors.initials: CM
authors.lastname: Chen
authors.forename: Feng-Ming
authors.initials: FM
authors.lastname: Yang
authors.forename: Meng-Chun
authors.initials: MC
authors.lastname: Hu
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D008807:Mice, Inbred BALB C; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D000779:Anesthetics, Local