Arsenic trioxide sensitizes CD95/Fas‐induced apoptosis through ROS‐mediated upregulation of CD95/Fas by NF‐κB activation
CD95/Fas is a cell surface protein that belongs to the tumor necrosis factor receptor family. Signals through CD95/Fas are able to induce apoptosis in sensitive cells. Therefore, modalities to regulate the CD95/Fas expression level in tumor cells are called for. In the present study, we show that su...
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Published in | International journal of cancer Vol. 112; no. 4; pp. 596 - 606 |
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Main Authors | , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
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20.11.2004
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Abstract | CD95/Fas is a cell surface protein that belongs to the tumor necrosis factor receptor family. Signals through CD95/Fas are able to induce apoptosis in sensitive cells. Therefore, modalities to regulate the CD95/Fas expression level in tumor cells are called for. In the present study, we show that sublethal doses of arsenic trioxide (As2O3) sensitized CD95/Fas‐induced apoptosis in human cervical cancer cells, and the sensitizing effects resulted from As2O3‐mediated increase in the expression of the CD95/Fas. N‐acetyl‐L‐cysteine, a specific scavenger of reactive oxygen species, abrogated As2O3‐induced upregulation of CD95/Fas and enhancement of CD95/Fas‐mediated apoptosis. Furthermore, inhibition of NF‐κB by transient transfection of IκBα supersuppressor blocked the increase of CD95/Fas expression following As2O3 treatment. Antisense oligonucleotide of CD95/Fas and ZB4, an antibody that blocks the binding of CD95/Fas ligand to CD95/Fas, reduced the amount of As2O3‐sensitized CD95/Fas‐induced apoptosis, demonstrating the specificity of CD95/Fas‐binding ligands in the As2O3‐sensitized CD95/Fas‐induced apoptosis. These findings demonstrate that sensitization of human cervical cancer cells to CD95/Fas‐mediated apoptosis by As2O3 can be partly due to induction of ROS and subsequent upregulation of CD95/Fas gene expression by NF‐κB activation. © 2004 Wiley‐Liss, Inc. |
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AbstractList | Abstract
CD95/Fas is a cell surface protein that belongs to the tumor necrosis factor receptor family. Signals through CD95/Fas are able to induce apoptosis in sensitive cells. Therefore, modalities to regulate the CD95/Fas expression level in tumor cells are called for. In the present study, we show that sublethal doses of arsenic trioxide (As
2
O
3
) sensitized CD95/Fas‐induced apoptosis in human cervical cancer cells, and the sensitizing effects resulted from As
2
O
3
‐mediated increase in the expression of the CD95/Fas. N‐acetyl‐
L
‐cysteine, a specific scavenger of reactive oxygen species, abrogated As
2
O
3
‐induced upregulation of CD95/Fas and enhancement of CD95/Fas‐mediated apoptosis. Furthermore, inhibition of NF‐κB by transient transfection of IκBα supersuppressor blocked the increase of CD95/Fas expression following As
2
O
3
treatment. Antisense oligonucleotide of CD95/Fas and ZB4, an antibody that blocks the binding of CD95/Fas ligand to CD95/Fas, reduced the amount of As
2
O
3
‐sensitized CD95/Fas‐induced apoptosis, demonstrating the specificity of CD95/Fas‐binding ligands in the As
2
O
3
‐sensitized CD95/Fas‐induced apoptosis. These findings demonstrate that sensitization of human cervical cancer cells to CD95/Fas‐mediated apoptosis by As
2
O
3
can be partly due to induction of ROS and subsequent upregulation of CD95/Fas gene expression by NF‐κB activation. © 2004 Wiley‐Liss, Inc. CD95/Fas is a cell surface protein that belongs to the tumor necrosis factor receptor family. Signals through CD95/Fas are able to induce apoptosis in sensitive cells. Therefore, modalities to regulate the CD95/Fas expression level in tumor cells are called for. In the present study, we show that sublethal doses of arsenic trioxide (As2O3) sensitized CD95/Fas‐induced apoptosis in human cervical cancer cells, and the sensitizing effects resulted from As2O3‐mediated increase in the expression of the CD95/Fas. N‐acetyl‐L‐cysteine, a specific scavenger of reactive oxygen species, abrogated As2O3‐induced upregulation of CD95/Fas and enhancement of CD95/Fas‐mediated apoptosis. Furthermore, inhibition of NF‐κB by transient transfection of IκBα supersuppressor blocked the increase of CD95/Fas expression following As2O3 treatment. Antisense oligonucleotide of CD95/Fas and ZB4, an antibody that blocks the binding of CD95/Fas ligand to CD95/Fas, reduced the amount of As2O3‐sensitized CD95/Fas‐induced apoptosis, demonstrating the specificity of CD95/Fas‐binding ligands in the As2O3‐sensitized CD95/Fas‐induced apoptosis. These findings demonstrate that sensitization of human cervical cancer cells to CD95/Fas‐mediated apoptosis by As2O3 can be partly due to induction of ROS and subsequent upregulation of CD95/Fas gene expression by NF‐κB activation. © 2004 Wiley‐Liss, Inc. |
Author | Lee, Su‐Jae Lee, Hyung‐Chahn Park, Myung‐Jin Gwak, Ho‐Shin Park, In‐Chul Cho, Hyeyoung Jin, Hyeon‐Ok An, Sungkwan Hong, Seok‐Il Park, Sin‐Ae Woo, Sang Hyeok Rhee, Chang Hun Hong, Young‐Joon |
Author_xml | – sequence: 1 givenname: Sang Hyeok surname: Woo fullname: Woo, Sang Hyeok – sequence: 2 givenname: In‐Chul surname: Park fullname: Park, In‐Chul – sequence: 3 givenname: Myung‐Jin surname: Park fullname: Park, Myung‐Jin – sequence: 4 givenname: Sungkwan surname: An fullname: An, Sungkwan – sequence: 5 givenname: Hyung‐Chahn surname: Lee fullname: Lee, Hyung‐Chahn – sequence: 6 givenname: Hyeon‐Ok surname: Jin fullname: Jin, Hyeon‐Ok – sequence: 7 givenname: Sin‐Ae surname: Park fullname: Park, Sin‐Ae – sequence: 8 givenname: Hyeyoung surname: Cho fullname: Cho, Hyeyoung – sequence: 9 givenname: Su‐Jae surname: Lee fullname: Lee, Su‐Jae – sequence: 10 givenname: Ho‐Shin surname: Gwak fullname: Gwak, Ho‐Shin – sequence: 11 givenname: Young‐Joon surname: Hong fullname: Hong, Young‐Joon – sequence: 12 givenname: Seok‐Il surname: Hong fullname: Hong, Seok‐Il – sequence: 13 givenname: Chang Hun surname: Rhee fullname: Rhee, Chang Hun email: changhun@kcch.re.kr |
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Keywords | Antineoplastic agent Human Reactive oxygen species Arsenic trioxide Malignant tumor Gene expression In vitro Hela cell line Biological activity Female genital diseases Cancerology Cell death Established cell line Fas Antigen Sensitization Transcription factor NFκB Uterine cervix diseases Cervical cancer Apoptosis |
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Snippet | CD95/Fas is a cell surface protein that belongs to the tumor necrosis factor receptor family. Signals through CD95/Fas are able to induce apoptosis in... Abstract CD95/Fas is a cell surface protein that belongs to the tumor necrosis factor receptor family. Signals through CD95/Fas are able to induce apoptosis in... |
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SubjectTerms | Antineoplastic agents apoptosis arsenic trioxide Biological and medical sciences CD95/Fas General aspects Medical sciences NF‐κB Pharmacology. Drug treatments reactive oxygen species Tumors |
Title | Arsenic trioxide sensitizes CD95/Fas‐induced apoptosis through ROS‐mediated upregulation of CD95/Fas by NF‐κB activation |
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