title: Bupivacaine induces apoptosis through caspase-dependent and -independent pathways in canine mammary tumor cells.
abstract: Local anesthetics have been reported to induce apoptosis in various cell lines. In this study, we showed that bupivacaine also induced apoptosis in DTK-SME cells, a vimentin(+)/AE1(+)/CK7(+)/HSP27(+), tumorigenic, immortalized, canine mammary tumor cell line. Bupivacaine induced apoptosis in DTK-SME cells in a time- and concentration-dependent manner. Apoptosis-associated morphological changes, including cell shrinkage and rounding, chromatin condensation, and formation of apoptotic bodies, were observed in the bupivacaine-treated DTK-SME cells. Apoptosis was further confirmed with annexin V staining, TUNEL staining, and DNA laddering assays. At the molecular level, the activation of caspases-3, -8, and -9 corresponded well to the degree of DNA fragmentation triggered by bupivacaine. We also demonstrated that the pan-caspase inhibitor, z-VAD-fmk, only partially inhibited the apoptosis induced by bupivacaine. Moreover, treated cells increased expression of endonuclease G, a death effector that acts independently of caspases. Our data suggested that bupivacaine-induced apoptosis occurs through both caspase-dependent and caspase-independent apoptotic pathways.
authors.affiliation: Department of Biotechnology and Animal Science, National Ilan University, Yilan, Taiwan.
authors.forename: Yi-Shu
authors.initials: YS
authors.lastname: Chiu
authors.affiliation: Department of Biotechnology and Animal Science, National Ilan University, Yilan, Taiwan.
authors.forename: Yeong-Hsiang
authors.initials: YH
authors.lastname: Cheng
authors.affiliation: Department of Nursing, Cardinal Tien College of Healthcare & Management, Sindian, Taiwan.
authors.forename: Sui-Wen
authors.initials: SW
authors.lastname: Lin
authors.affiliation: Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Chiayi, Taiwan.
authors.forename: Te-Sheng
authors.initials: TS
authors.lastname: Chang
authors.affiliation: Department of Nursing, Chang Gung University of Science and Technology, Taoyuan, Taiwan; Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan.
authors.forename: Chian-Jiun
authors.initials: CJ
authors.lastname: Liou
authors.affiliation: Department of Biotechnology and Animal Science, National Ilan University, Yilan, Taiwan. Electronic address: yslai@niu.edu.tw.
authors.forename: Yu-Shen
authors.initials: YS
authors.lastname: Lai
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002045:Bupivacaine / Q000494:pharmacology*; D061945:Caspase Inhibitors / Q000378:metabolism; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D053938:DNA Fragmentation / Q000187:drug effects; D004283:Dog Diseases / Q000188:drug therapy* / Q000209:etiology; D004285:Dogs; D005260:Female; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy* / Q000209:etiology
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D000970:Antineoplastic Agents; D061945:Caspase Inhibitors; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D020169:Caspases; D002045:Bupivacaine
keywords: Anesthetic; Apoptosis; Bupivacaine; Canine mammary tumor cell