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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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Blackwell Publishing Ltd
2001
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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. |
format | Online Article Text |
id | pubmed-5926847 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2001 |
publisher | Blackwell Publishing Ltd |
record_format | MEDLINE/PubMed |
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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