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Combined use of irinotecan and p53 activator enhances growth inhibition of mesothelioma cells

Malignant mesothelioma (MM) is an aggressive malignant neoplasm which rapidly invades pleural tissues and has a poor prognosis. Here, we explore enhancement of the effect of irinotecan [camptothecin‐11 (CPT‐11)] by the p53‐dependent induction of carboxylesterase 2 (CES2), a CPT‐11‐activating enzyme,...

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Autores principales: Han, Bo, Lee‐Okada, Hyeon‐Cheol, Ishimine, Momoko, Orita, Hajime, Nishikawa, Keiko, Takagaki, Tetsuya, Kajino, Kazunori, Yokomizo, Takehiko, Hino, Okio, Kobayashi, Toshiyuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609812/
https://www.ncbi.nlm.nih.gov/pubmed/32961616
http://dx.doi.org/10.1002/2211-5463.12985
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author Han, Bo
Lee‐Okada, Hyeon‐Cheol
Ishimine, Momoko
Orita, Hajime
Nishikawa, Keiko
Takagaki, Tetsuya
Kajino, Kazunori
Yokomizo, Takehiko
Hino, Okio
Kobayashi, Toshiyuki
author_facet Han, Bo
Lee‐Okada, Hyeon‐Cheol
Ishimine, Momoko
Orita, Hajime
Nishikawa, Keiko
Takagaki, Tetsuya
Kajino, Kazunori
Yokomizo, Takehiko
Hino, Okio
Kobayashi, Toshiyuki
author_sort Han, Bo
collection PubMed
description Malignant mesothelioma (MM) is an aggressive malignant neoplasm which rapidly invades pleural tissues and has a poor prognosis. Here, we explore enhancement of the effect of irinotecan [camptothecin‐11 (CPT‐11)] by the p53‐dependent induction of carboxylesterase 2 (CES2), a CPT‐11‐activating enzyme, in MM. The level of CES2 mRNA was greatly increased on treatment with nutlin‐3a. A combination of CPT‐11 and nutlin‐3a inhibited the growth of MM cells more effectively than either drug alone. Knocking down CES2 in MM cells reduced the effect of the drug combination, and its forced expression in MESO4 cells enhanced the growth inhibitory activity of CPT‐11 in the absence of nutlin‐3a. Enhancement of the growth inhibitory activity of CPT‐11 by nutlin‐3a suggests a possible new combinatorial MM chemotherapy regimen.
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spelling pubmed-76098122020-11-06 Combined use of irinotecan and p53 activator enhances growth inhibition of mesothelioma cells Han, Bo Lee‐Okada, Hyeon‐Cheol Ishimine, Momoko Orita, Hajime Nishikawa, Keiko Takagaki, Tetsuya Kajino, Kazunori Yokomizo, Takehiko Hino, Okio Kobayashi, Toshiyuki FEBS Open Bio Research Articles Malignant mesothelioma (MM) is an aggressive malignant neoplasm which rapidly invades pleural tissues and has a poor prognosis. Here, we explore enhancement of the effect of irinotecan [camptothecin‐11 (CPT‐11)] by the p53‐dependent induction of carboxylesterase 2 (CES2), a CPT‐11‐activating enzyme, in MM. The level of CES2 mRNA was greatly increased on treatment with nutlin‐3a. A combination of CPT‐11 and nutlin‐3a inhibited the growth of MM cells more effectively than either drug alone. Knocking down CES2 in MM cells reduced the effect of the drug combination, and its forced expression in MESO4 cells enhanced the growth inhibitory activity of CPT‐11 in the absence of nutlin‐3a. Enhancement of the growth inhibitory activity of CPT‐11 by nutlin‐3a suggests a possible new combinatorial MM chemotherapy regimen. John Wiley and Sons Inc. 2020-10-05 /pmc/articles/PMC7609812/ /pubmed/32961616 http://dx.doi.org/10.1002/2211-5463.12985 Text en © 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd. This is an open access article under the terms of the 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 Research Articles
Han, Bo
Lee‐Okada, Hyeon‐Cheol
Ishimine, Momoko
Orita, Hajime
Nishikawa, Keiko
Takagaki, Tetsuya
Kajino, Kazunori
Yokomizo, Takehiko
Hino, Okio
Kobayashi, Toshiyuki
Combined use of irinotecan and p53 activator enhances growth inhibition of mesothelioma cells
title Combined use of irinotecan and p53 activator enhances growth inhibition of mesothelioma cells
title_full Combined use of irinotecan and p53 activator enhances growth inhibition of mesothelioma cells
title_fullStr Combined use of irinotecan and p53 activator enhances growth inhibition of mesothelioma cells
title_full_unstemmed Combined use of irinotecan and p53 activator enhances growth inhibition of mesothelioma cells
title_short Combined use of irinotecan and p53 activator enhances growth inhibition of mesothelioma cells
title_sort combined use of irinotecan and p53 activator enhances growth inhibition of mesothelioma cells
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609812/
https://www.ncbi.nlm.nih.gov/pubmed/32961616
http://dx.doi.org/10.1002/2211-5463.12985
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