Augmented adriamycin sensitivity in cells transduced with an antisense tumor necrosis factor gene is mediated by caspase-3 downstream from reactive oxygen species

Citation
M. Sasaki et al., Augmented adriamycin sensitivity in cells transduced with an antisense tumor necrosis factor gene is mediated by caspase-3 downstream from reactive oxygen species, JPN J CANC, 92(9), 2001, pp. 983-988
Citations number
21
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
JAPANESE JOURNAL OF CANCER RESEARCH
ISSN journal
0910-5050 → ACNP
Volume
92
Issue
9
Year of publication
2001
Pages
983 - 988
Database
ISI
SICI code
0910-5050(200109)92:9<983:AASICT>2.0.ZU;2-D
Abstract
While transduction of an antisense tumor necrosis factor (TNF) gene sequenc e can augment the cytotoxicity of adriamycin (ADM) in human cancer cells, t he specific effect of introducing this sequence on the signal transduction pathway leading to cell death remains unclear. In ADM-resistant pancreatic carcinoma (PANC-1) cells, both the antioxidant N-acetyl-L-cysteine (NAC) an d the caspase-3 inhibitor acetyl-L-aspartyl-L-Methionyl-L-glutaminyl-L-aspa rtyl-aldehyde (Ac-DMQD-CHO) prevented ADM-induced cytotoxicity. NAC additio nally inhibited caspase-3 activity induced by ADM treatment, while Ac-DMQD- CHO showed no suppressive effect on reactive oxygen species (ROS). Stable a ntisense-TNF transfectants showed higher ADM sensitivity and greater ADM-in duced ROS production and caspase-3 activity than mock transfectant or paren t cells. These results indicate that increased caspase-3 activity downstrea m from ROS production is among the mechanisms by which transduction of the antisense TNF sequence of augments ADM sensitivity of pancreatic carcinoma cells.