title: Local anesthetic bupivacaine induced ovarian and prostate cancer apoptotic cell death and underlying mechanisms in vitro.
abstract: Retrospective studies indicate that the use of regional anesthesia can reduce cancer recurrence after surgery which could be due to ranging from immune function preservation to direct molecular mechanisms. This study was to investigate the effects of bupivacaine on ovarian and prostate cancer cell biology and the underlying molecular mechanisms. Cell viability, proliferation and migration of ovarian carcinoma (SKOV-3) and prostate carcinoma (PC-3) were examined following treatment with bupivacaine. Cleaved caspase 3, 8 and 9, and GSK-3β, pGSK-3β(tyr216) and pGSK-3β(ser9) expression were assessed by immunofluorescence. FAS ligand neutralization, caspase and GSK-3 inhibitors and GSK-3β siRNA were applied to further explore underlying mechanisms. Clinically relevant concentrations of bupivacaine reduced cell viability and inhibited cellular proliferation and migration in both cell lines. Caspase 8 and 9 inhibition generated partial cell death reversal in SKOV-3, whilst only caspase 9 was effective in PC-3. Bupivacaine increased the phosphorylation of GSK-3β(Tyr216) in SKOV-3 but without measurable effect in PC3. GSK-3β inhibition and siRNA gene knockdown decreased bupivacaine induced cell death in SKOV-3 but not in PC3. Our data suggests that bupivacaine has direct 'anti-cancer' properties through the activation of intrinsic and extrinsic apoptotic pathways in ovarian cancer but only the intrinsic pathway in prostate cancer.
authors.affiliation: Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200001, China.|Institute of Anesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhoung University of Science and Technology, Wuhan, Hubei, China.|Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea &Westminster Hospital, London, UK.
authors.forename: Wei
authors.initials: W
authors.lastname: Xuan
authors.affiliation: Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea &Westminster Hospital, London, UK.
authors.forename: Hailin
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea &Westminster Hospital, London, UK.
authors.forename: James
authors.initials: J
authors.lastname: Hankin
authors.affiliation: Institute of Anesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhoung University of Science and Technology, Wuhan, Hubei, China.|Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea &Westminster Hospital, London, UK.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.affiliation: Institute of Anesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhoung University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Shanglong
authors.initials: S
authors.lastname: Yao
authors.affiliation: Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea &Westminster Hospital, London, UK.
authors.forename: Daqing
authors.initials: D
authors.lastname: Ma
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002045:Bupivacaine / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D038341:Glycogen Synthase Kinases / Q000378:metabolism; D006801:Humans; D008297:Male; D010051:Ovarian Neoplasms; D011471:Prostatic Neoplasms; D034622:RNA Interference
chemical_list: D000779:Anesthetics, Local; D038341:Glycogen Synthase Kinases; D020169:Caspases; D002045:Bupivacaine