Cargando…

Calpain‐2 inhibitor treatment preferentially reduces tumor progression for human colon cancer cells expressing highest levels of this enzyme

Calpain‐2 levels are higher in colorectal tumors resistant to chemotherapy and previous work showed calpain‐2 inhibitor therapy reduced inflammation‐driven colorectal cancer, but direct effects of the inhibitor on colon cancer cells themselves were not demonstrated. In the present study, five human...

Descripción completa

Detalles Bibliográficos
Autores principales: Marciel, Michael P., Rose, Aaron H., Martinez, Verena, Horio, David T., Hashimoto, Ann S., Hoffmann, FuKun W., Bertino, Pietro, Hoffmann, Peter R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5773958/
https://www.ncbi.nlm.nih.gov/pubmed/29210197
http://dx.doi.org/10.1002/cam4.1260
_version_ 1783293672686616576
author Marciel, Michael P.
Rose, Aaron H.
Martinez, Verena
Horio, David T.
Hashimoto, Ann S.
Hoffmann, FuKun W.
Bertino, Pietro
Hoffmann, Peter R.
author_facet Marciel, Michael P.
Rose, Aaron H.
Martinez, Verena
Horio, David T.
Hashimoto, Ann S.
Hoffmann, FuKun W.
Bertino, Pietro
Hoffmann, Peter R.
author_sort Marciel, Michael P.
collection PubMed
description Calpain‐2 levels are higher in colorectal tumors resistant to chemotherapy and previous work showed calpain‐2 inhibitor therapy reduced inflammation‐driven colorectal cancer, but direct effects of the inhibitor on colon cancer cells themselves were not demonstrated. In the present study, five human colon cancer cell lines were directly treated with a calpain‐2 inhibitor and results showed increased cell death in 4 of 5 cell lines and decreased anchorage‐independent growth for all cell five lines. When tested for levels of calpain‐2, three cell lines exhibited increasing levels of this enzyme: HCT15 (low), HCC2998 (medium), and HCT116 (significantly higher). This was consistent with gel shift assays showing that calpain‐2 inhibitor reduced of NF‐κB nuclear translocation most effectively in HCT116 cells. Ability of calpain‐2 inhibitor to impede tumor progression in vivo was evaluated using intrarectal transplant of luciferase‐expressing cells for these three cell lines. Results showed that calpain‐2 inhibitor therapy reduced tumor growth and increased survival only in mice injected with HCT116 cells. These data suggest calpain‐2 inhibitor treatment may be most effective on colorectal tumors expressing highest levels of calpain‐2.
format Online
Article
Text
id pubmed-5773958
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-57739582018-02-07 Calpain‐2 inhibitor treatment preferentially reduces tumor progression for human colon cancer cells expressing highest levels of this enzyme Marciel, Michael P. Rose, Aaron H. Martinez, Verena Horio, David T. Hashimoto, Ann S. Hoffmann, FuKun W. Bertino, Pietro Hoffmann, Peter R. Cancer Med Cancer Biology Calpain‐2 levels are higher in colorectal tumors resistant to chemotherapy and previous work showed calpain‐2 inhibitor therapy reduced inflammation‐driven colorectal cancer, but direct effects of the inhibitor on colon cancer cells themselves were not demonstrated. In the present study, five human colon cancer cell lines were directly treated with a calpain‐2 inhibitor and results showed increased cell death in 4 of 5 cell lines and decreased anchorage‐independent growth for all cell five lines. When tested for levels of calpain‐2, three cell lines exhibited increasing levels of this enzyme: HCT15 (low), HCC2998 (medium), and HCT116 (significantly higher). This was consistent with gel shift assays showing that calpain‐2 inhibitor reduced of NF‐κB nuclear translocation most effectively in HCT116 cells. Ability of calpain‐2 inhibitor to impede tumor progression in vivo was evaluated using intrarectal transplant of luciferase‐expressing cells for these three cell lines. Results showed that calpain‐2 inhibitor therapy reduced tumor growth and increased survival only in mice injected with HCT116 cells. These data suggest calpain‐2 inhibitor treatment may be most effective on colorectal tumors expressing highest levels of calpain‐2. John Wiley and Sons Inc. 2017-12-06 /pmc/articles/PMC5773958/ /pubmed/29210197 http://dx.doi.org/10.1002/cam4.1260 Text en © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Cancer Biology
Marciel, Michael P.
Rose, Aaron H.
Martinez, Verena
Horio, David T.
Hashimoto, Ann S.
Hoffmann, FuKun W.
Bertino, Pietro
Hoffmann, Peter R.
Calpain‐2 inhibitor treatment preferentially reduces tumor progression for human colon cancer cells expressing highest levels of this enzyme
title Calpain‐2 inhibitor treatment preferentially reduces tumor progression for human colon cancer cells expressing highest levels of this enzyme
title_full Calpain‐2 inhibitor treatment preferentially reduces tumor progression for human colon cancer cells expressing highest levels of this enzyme
title_fullStr Calpain‐2 inhibitor treatment preferentially reduces tumor progression for human colon cancer cells expressing highest levels of this enzyme
title_full_unstemmed Calpain‐2 inhibitor treatment preferentially reduces tumor progression for human colon cancer cells expressing highest levels of this enzyme
title_short Calpain‐2 inhibitor treatment preferentially reduces tumor progression for human colon cancer cells expressing highest levels of this enzyme
title_sort calpain‐2 inhibitor treatment preferentially reduces tumor progression for human colon cancer cells expressing highest levels of this enzyme
topic Cancer Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5773958/
https://www.ncbi.nlm.nih.gov/pubmed/29210197
http://dx.doi.org/10.1002/cam4.1260
work_keys_str_mv AT marcielmichaelp calpain2inhibitortreatmentpreferentiallyreducestumorprogressionforhumancoloncancercellsexpressinghighestlevelsofthisenzyme
AT roseaaronh calpain2inhibitortreatmentpreferentiallyreducestumorprogressionforhumancoloncancercellsexpressinghighestlevelsofthisenzyme
AT martinezverena calpain2inhibitortreatmentpreferentiallyreducestumorprogressionforhumancoloncancercellsexpressinghighestlevelsofthisenzyme
AT horiodavidt calpain2inhibitortreatmentpreferentiallyreducestumorprogressionforhumancoloncancercellsexpressinghighestlevelsofthisenzyme
AT hashimotoanns calpain2inhibitortreatmentpreferentiallyreducestumorprogressionforhumancoloncancercellsexpressinghighestlevelsofthisenzyme
AT hoffmannfukunw calpain2inhibitortreatmentpreferentiallyreducestumorprogressionforhumancoloncancercellsexpressinghighestlevelsofthisenzyme
AT bertinopietro calpain2inhibitortreatmentpreferentiallyreducestumorprogressionforhumancoloncancercellsexpressinghighestlevelsofthisenzyme
AT hoffmannpeterr calpain2inhibitortreatmentpreferentiallyreducestumorprogressionforhumancoloncancercellsexpressinghighestlevelsofthisenzyme