Local anesthetic bupivacaine induced ovarian and prostate cancer apoptotic cell death and underlying mechanisms in vitro

• Published in: Scientific reports 2016-05, Vol.6 (1), p.26277-26277, Article 26277
• Main Authors: Xuan, Wei, Zhao, Hailin, Hankin, James, Chen, Lin, Yao, Shanglong, Ma, Daqing
• Format: Article
• Language: English
• Subjects: 14; 14/34; 42/41; 631/67/322; 692/308/575; 96/2; Anesthesia; Anesthetics, Local - pharmacology; Apoptosis; Apoptosis - drug effects; Bupivacaine; Bupivacaine - pharmacology; Caspase; Caspase-3; Caspase-8; Caspase-9; Caspases - metabolism; Cell death; Cell Line, Tumor; Cell Movement - drug effects; Cell Proliferation - drug effects; Cell Survival - drug effects; FasL protein; Female; Glycogen Synthase Kinases - metabolism; Humanities and Social Sciences; Humans; Immune response; Immunofluorescence; Local anesthesia; Male; Molecular modelling; Mortality; multidisciplinary; Neutralization; Ovarian cancer; Ovarian carcinoma; Ovarian Neoplasms; Phosphorylation; Preservation; Prostate cancer; Prostate carcinoma; Prostatic Neoplasms; RNA Interference; Science; siRNA; Surgery
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep26277

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.