Augmented Adriamycin Sensitivity in Cells Transduced with an Antisense Tumor Necrosis Factor Gene Is Mediated by Caspase-3 Downstream from Reactive Oxygen Species
- 1 September 2001
- journal article
- Published by Wiley in Japanese Journal of Cancer Research
- Vol. 92 (9) , 983-988
- https://doi.org/10.1111/j.1349-7006.2001.tb01189.x
Abstract
While transduction of an antisense tumor necrosis factor (TNF) gene sequence can augment the cytotoxicity of adriamycin (ADM) in human cancer cells, the 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) and the caspase‐3 inhibitor acetyl‐L‐aspartyl‐L‐methionyl‐L‐glutaminyl‐L‐aspartyl‐aldehyde (Ac‐DMQD‐CHO) prevented ADM‐induced cytotoxicity. NAC additionally inhibited caspase‐3 activity induced by ADM treatment, while Ac‐DMQD‐CHO showed no suppressive effect on reactive oxygen species (ROS). Stable antisense‐TNF transfectants showed higher ADM sensitivity and greater ADM‐induced ROS production and caspase‐3 activity than mock transfectant or parent cells. These results indicate that increased caspase‐3 activity downstream from ROS production is among the mechanisms by which transduction of the antisense TNF sequence of augments ADM sensitivity of pancreatic carcinoma cells.Keywords
This publication has 23 references indexed in Scilit:
- Caspase-3 Activation Downstream from Reactive Oxygen Species in Heat-Induced Apoptosis of Pancreatic Carcinoma Cells Carrying a Mutant p53 GenePancreas, 2001
- Doxorubicin Treatment Activates a Z-VAD-Sensitive Caspase, Which Causes ΔΨm Loss, Caspase-9 Activity, and Apoptosis in Jurkat CellsExperimental Cell Research, 2000
- Proteolytic Cleavage and Activation of Protein Kinase C μ by Caspase-3 in the Apoptotic Response of Cells to 1-β-d-Arabinofuranosylcytosine and Other Genotoxic AgentsJournal of Biological Chemistry, 2000
- Hsp70 exerts its anti-apoptotic function downstream of caspase-3-like proteasesThe EMBO Journal, 1998
- Activation of the CD95 (APO-1/Fas) pathway in drug- and γ-irradiation-induced apoptosis of brain tumor cellsCell Death & Differentiation, 1998
- The CD95/CD95 ligand system is not the major effector in anticancer drug-mediated apoptosisCell Death & Differentiation, 1998
- Induction of heat shock protein 72 synthesis by endogenous tumor necrosis factor via enhancement of the heat shock element-binding activity of heat shock factor 1European Journal of Immunology, 1997
- Endogenous Tumor Necrosis Factor Functions as a Resistant Factor against Hyperthermic Cytotoxicity in Pancreatic Carcinoma Cells via Enhancement of the Heat Shock Element-Binding Activity of Heat Shock Factor 1Chemotherapy, 1997
- Endogenous Tumor Necrosis Factor Inhibits the Cytotoxicity of Exogenous Tumor Necrosis Factor and Adriamycin in Pancreatic Carcinoma CellsPancreas, 1996
- Endogenous tumor necrosis factor functions as a resistant factor against adriamycinInternational Journal of Cancer, 1994