Bupivacaine induces apoptosis through caspase-dependent and -independent pathways in canine mammary tumor cells.
Res Vet Sci
; 100: 232-8, 2015 Jun.
Article
in En
| MEDLINE
| ID: mdl-25843897
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Bupivacaine
/
Mammary Neoplasms, Animal
/
Apoptosis
/
Caspases
/
Dog Diseases
/
Antineoplastic Agents
Type of study:
Etiology_studies
Limits:
Animals
Language:
En
Journal:
Res Vet Sci
Year:
2015
Document type:
Article
Affiliation country:
Taiwán