Bupivacaine induces apoptosis through caspase-dependent and -independent pathways in canine mammary tumor cells. (June 2015)

• Record Type: Journal Article
• Authors: Chiu, Yi-Shu; Cheng, Yeong-Hsiang; Lin, Sui-Wen; Chang, Te-Sheng; Liou, Chian-Jiun; Lai, Yu-Shen
• Is Part Of: Research in veterinary science. Volume 100(2015)
• Page Start: 232
• Page End: 238
• Publication Date: 2015-06
• Subjects: Anesthetic -- Apoptosis -- Bupivacaine -- Canine mammary tumor cell; Veterinary medicine -- Periodicals; Veterinary Medicine -- Periodicals; Médecine vétérinaire -- Périodiques; Médecine vétérinaire -- Recherche -- Périodiques; Diergeneeskunde; 636.089
• DOI: 10.1016/j.rvsc.2015.03.024
• Languages: English
• ISSNs: 0034-5288

Abstract

Highlights: Bupivacaine induced apoptosis in DTK-SME, a canine mammary cancer cell line. Bupivacaine induced apoptosis in DTK-SME in a time- and dose-dependent manner. The apoptosis pathways included the extrinsic caspase-dependent pathway. Mitochondria-regulated caspase-dependent and -independent pathways were activated. Mitochondria play an important role in bupivacaine-induced apoptosis in DTK-SME. 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.