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Augmented Adriamycin Sensitivity in Cells Transduced with an Antisense Tumor Necrosis Factor Gene Is Mediated by Caspase‐3 Downstream from Reactive Oxygen Species

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...

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Detalles Bibliográficos
Autores principales: Sasaki, Masahiro, Kobayashi, Daisuke, Watanabe, Naoki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2001
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5926847/
https://www.ncbi.nlm.nih.gov/pubmed/11572767
http://dx.doi.org/10.1111/j.1349-7006.2001.tb01189.x
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author Sasaki, Masahiro
Kobayashi, Daisuke
Watanabe, Naoki
author_facet Sasaki, Masahiro
Kobayashi, Daisuke
Watanabe, Naoki
author_sort Sasaki, Masahiro
collection PubMed
description 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.
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spelling pubmed-59268472018-05-11 Augmented Adriamycin Sensitivity in Cells Transduced with an Antisense Tumor Necrosis Factor Gene Is Mediated by Caspase‐3 Downstream from Reactive Oxygen Species Sasaki, Masahiro Kobayashi, Daisuke Watanabe, Naoki Jpn J Cancer Res Article 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. Blackwell Publishing Ltd 2001-09 /pmc/articles/PMC5926847/ /pubmed/11572767 http://dx.doi.org/10.1111/j.1349-7006.2001.tb01189.x Text en
spellingShingle Article
Sasaki, Masahiro
Kobayashi, Daisuke
Watanabe, Naoki
Augmented Adriamycin Sensitivity in Cells Transduced with an Antisense Tumor Necrosis Factor Gene Is Mediated by Caspase‐3 Downstream from Reactive Oxygen Species
title Augmented Adriamycin Sensitivity in Cells Transduced with an Antisense Tumor Necrosis Factor Gene Is Mediated by Caspase‐3 Downstream from Reactive Oxygen Species
title_full Augmented Adriamycin Sensitivity in Cells Transduced with an Antisense Tumor Necrosis Factor Gene Is Mediated by Caspase‐3 Downstream from Reactive Oxygen Species
title_fullStr Augmented Adriamycin Sensitivity in Cells Transduced with an Antisense Tumor Necrosis Factor Gene Is Mediated by Caspase‐3 Downstream from Reactive Oxygen Species
title_full_unstemmed Augmented Adriamycin Sensitivity in Cells Transduced with an Antisense Tumor Necrosis Factor Gene Is Mediated by Caspase‐3 Downstream from Reactive Oxygen Species
title_short Augmented Adriamycin Sensitivity in Cells Transduced with an Antisense Tumor Necrosis Factor Gene Is Mediated by Caspase‐3 Downstream from Reactive Oxygen Species
title_sort augmented adriamycin sensitivity in cells transduced with an antisense tumor necrosis factor gene is mediated by caspase‐3 downstream from reactive oxygen species
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5926847/
https://www.ncbi.nlm.nih.gov/pubmed/11572767
http://dx.doi.org/10.1111/j.1349-7006.2001.tb01189.x
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