Yuan-Ching Chang1, Chien-Liang Liu, Ming-Jen Chen, Yung-Wei Hsu, Shan-Na Chen, Chi-Hsin Lin, Chin-Man Chen, Feng-Ming Yang, Meng-Chun Hu. 1. 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.
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. CONCLUSION: 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.
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 humanbreast tumor cells. METHODS:Humanbreast 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. CONCLUSION: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.