Eintrag weiter verarbeiten
Cytotoxic synergy between the multikinase inhibitor sorafenib and the proteasome inhibitor bortezomib in vitro: induction of apoptosis through Akt and c-Jun NH2-terminal kinase pat...
Gespeichert in:
Zeitschriftentitel: | Molecular Cancer Therapeutics |
---|---|
Personen und Körperschaften: | , , , , , , , , , |
In: | Molecular Cancer Therapeutics, 5, 2006, 9, S. 2378-2387 |
Format: | E-Article |
Sprache: | Englisch |
veröffentlicht: |
American Association for Cancer Research (AACR)
|
Schlagwörter: |
author_facet |
Yu, Chunrong Friday, Bret B. Lai, Jin-Ping Yang, Lin Sarkaria, Jann Kay, Neil E. Carter, Christopher A. Roberts, Lewis R. Kaufmann, Scott H. Adjei, Alex A. Yu, Chunrong Friday, Bret B. Lai, Jin-Ping Yang, Lin Sarkaria, Jann Kay, Neil E. Carter, Christopher A. Roberts, Lewis R. Kaufmann, Scott H. Adjei, Alex A. |
---|---|
author |
Yu, Chunrong Friday, Bret B. Lai, Jin-Ping Yang, Lin Sarkaria, Jann Kay, Neil E. Carter, Christopher A. Roberts, Lewis R. Kaufmann, Scott H. Adjei, Alex A. |
spellingShingle |
Yu, Chunrong Friday, Bret B. Lai, Jin-Ping Yang, Lin Sarkaria, Jann Kay, Neil E. Carter, Christopher A. Roberts, Lewis R. Kaufmann, Scott H. Adjei, Alex A. Molecular Cancer Therapeutics Cytotoxic synergy between the multikinase inhibitor sorafenib and the proteasome inhibitor bortezomib in vitro: induction of apoptosis through Akt and c-Jun NH2-terminal kinase pathways Cancer Research Oncology |
author_sort |
yu, chunrong |
spelling |
Yu, Chunrong Friday, Bret B. Lai, Jin-Ping Yang, Lin Sarkaria, Jann Kay, Neil E. Carter, Christopher A. Roberts, Lewis R. Kaufmann, Scott H. Adjei, Alex A. 1535-7163 1538-8514 American Association for Cancer Research (AACR) Cancer Research Oncology http://dx.doi.org/10.1158/1535-7163.mct-06-0235 <jats:title>Abstract</jats:title> <jats:p>This study was undertaken to characterize preclinical cytotoxic interactions for human malignancies between the multikinase inhibitor sorafenib (BAY 43-9006) and proteasome inhibitors bortezomib or MG132. Multiple tumor cell lines of varying histiotypes, including A549 (lung adenocarcinoma), 786-O (renal cell carcinoma), HeLa (cervical carcinoma), MDA-MB-231 (breast), K562 (chronic myelogenous leukemia), Jurkat (acute T-cell leukemia), MEC-2 (B-chronic lymphocytic leukemia), and U251 and D37 (glioma), as well as cells derived from primary human glioma tumors that are likely a more clinically relevant model were treated with sorafenib or bortezomib alone or in combination. Sorafenib and bortezomib synergistically induced a marked increase in mitochondrial injury and apoptosis, reflected by cytochrome c release, caspase-3 cleavage, and poly(ADP-ribose) polymerase degradation in a broad range of solid tumor and leukemia cell lines. These findings were accompanied by several biochemical changes, including decreased phosphorylation of vascular endothelial growth factor receptor-2, platelet-derived growth factor receptor-β, and Akt and increased phosphorylation of stress-related c-Jun NH2-terminal kinase (JNK). Inhibition of Akt was required for synergism, as a constitutively active Akt protected cells against apoptosis induced by the combination. Alternatively, the JNK inhibitor SP600125 could also protect cells from apoptosis induced by the combination, indicating that both inhibition of Akt and activation of JNK were required for the synergism. These findings show that sorafenib interacts synergistically with bortezomib to induce apoptosis in a broad spectrum of neoplastic cell lines and show an important role for the Akt and JNK pathways in mediating synergism. Further clinical development of this combination seems warranted. [Mol Cancer Ther 2006;5(9):2378–87]</jats:p> Cytotoxic synergy between the multikinase inhibitor sorafenib and the proteasome inhibitor bortezomib <i>in vitro</i>: induction of apoptosis through Akt and c-Jun NH2-terminal kinase pathways Molecular Cancer Therapeutics |
doi_str_mv |
10.1158/1535-7163.mct-06-0235 |
facet_avail |
Online Free |
finc_class_facet |
Medizin |
format |
ElectronicArticle |
fullrecord |
blob:ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTE1OC8xNTM1LTcxNjMubWN0LTA2LTAyMzU |
id |
ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTE1OC8xNTM1LTcxNjMubWN0LTA2LTAyMzU |
institution |
DE-Zi4 DE-Gla1 DE-15 DE-Pl11 DE-Rs1 DE-14 DE-105 DE-Ch1 DE-L229 DE-D275 DE-Bn3 DE-Brt1 DE-Zwi2 DE-D161 |
imprint |
American Association for Cancer Research (AACR), 2006 |
imprint_str_mv |
American Association for Cancer Research (AACR), 2006 |
issn |
1535-7163 1538-8514 |
issn_str_mv |
1535-7163 1538-8514 |
language |
English |
mega_collection |
American Association for Cancer Research (AACR) (CrossRef) |
match_str |
yu2006cytotoxicsynergybetweenthemultikinaseinhibitorsorafenibandtheproteasomeinhibitorbortezomibinvitroinductionofapoptosisthroughaktandcjunnh2terminalkinasepathways |
publishDateSort |
2006 |
publisher |
American Association for Cancer Research (AACR) |
recordtype |
ai |
record_format |
ai |
series |
Molecular Cancer Therapeutics |
source_id |
49 |
title |
Cytotoxic synergy between the multikinase inhibitor sorafenib and the proteasome inhibitor bortezomib in vitro: induction of apoptosis through Akt and c-Jun NH2-terminal kinase pathways |
title_unstemmed |
Cytotoxic synergy between the multikinase inhibitor sorafenib and the proteasome inhibitor bortezomib in vitro: induction of apoptosis through Akt and c-Jun NH2-terminal kinase pathways |
title_full |
Cytotoxic synergy between the multikinase inhibitor sorafenib and the proteasome inhibitor bortezomib in vitro: induction of apoptosis through Akt and c-Jun NH2-terminal kinase pathways |
title_fullStr |
Cytotoxic synergy between the multikinase inhibitor sorafenib and the proteasome inhibitor bortezomib in vitro: induction of apoptosis through Akt and c-Jun NH2-terminal kinase pathways |
title_full_unstemmed |
Cytotoxic synergy between the multikinase inhibitor sorafenib and the proteasome inhibitor bortezomib in vitro: induction of apoptosis through Akt and c-Jun NH2-terminal kinase pathways |
title_short |
Cytotoxic synergy between the multikinase inhibitor sorafenib and the proteasome inhibitor bortezomib in vitro: induction of apoptosis through Akt and c-Jun NH2-terminal kinase pathways |
title_sort |
cytotoxic synergy between the multikinase inhibitor sorafenib and the proteasome inhibitor bortezomib <i>in vitro</i>: induction of apoptosis through akt and c-jun nh2-terminal kinase pathways |
topic |
Cancer Research Oncology |
url |
http://dx.doi.org/10.1158/1535-7163.mct-06-0235 |
publishDate |
2006 |
physical |
2378-2387 |
description |
<jats:title>Abstract</jats:title>
<jats:p>This study was undertaken to characterize preclinical cytotoxic interactions for human malignancies between the multikinase inhibitor sorafenib (BAY 43-9006) and proteasome inhibitors bortezomib or MG132. Multiple tumor cell lines of varying histiotypes, including A549 (lung adenocarcinoma), 786-O (renal cell carcinoma), HeLa (cervical carcinoma), MDA-MB-231 (breast), K562 (chronic myelogenous leukemia), Jurkat (acute T-cell leukemia), MEC-2 (B-chronic lymphocytic leukemia), and U251 and D37 (glioma), as well as cells derived from primary human glioma tumors that are likely a more clinically relevant model were treated with sorafenib or bortezomib alone or in combination. Sorafenib and bortezomib synergistically induced a marked increase in mitochondrial injury and apoptosis, reflected by cytochrome c release, caspase-3 cleavage, and poly(ADP-ribose) polymerase degradation in a broad range of solid tumor and leukemia cell lines. These findings were accompanied by several biochemical changes, including decreased phosphorylation of vascular endothelial growth factor receptor-2, platelet-derived growth factor receptor-β, and Akt and increased phosphorylation of stress-related c-Jun NH2-terminal kinase (JNK). Inhibition of Akt was required for synergism, as a constitutively active Akt protected cells against apoptosis induced by the combination. Alternatively, the JNK inhibitor SP600125 could also protect cells from apoptosis induced by the combination, indicating that both inhibition of Akt and activation of JNK were required for the synergism. These findings show that sorafenib interacts synergistically with bortezomib to induce apoptosis in a broad spectrum of neoplastic cell lines and show an important role for the Akt and JNK pathways in mediating synergism. Further clinical development of this combination seems warranted. [Mol Cancer Ther 2006;5(9):2378–87]</jats:p> |
container_issue |
9 |
container_start_page |
2378 |
container_title |
Molecular Cancer Therapeutics |
container_volume |
5 |
format_de105 |
Article, E-Article |
format_de14 |
Article, E-Article |
format_de15 |
Article, E-Article |
format_de520 |
Article, E-Article |
format_de540 |
Article, E-Article |
format_dech1 |
Article, E-Article |
format_ded117 |
Article, E-Article |
format_degla1 |
E-Article |
format_del152 |
Buch |
format_del189 |
Article, E-Article |
format_dezi4 |
Article |
format_dezwi2 |
Article, E-Article |
format_finc |
Article, E-Article |
format_nrw |
Article, E-Article |
_version_ |
1792338352864755720 |
geogr_code |
not assigned |
last_indexed |
2024-03-01T15:30:52.835Z |
geogr_code_person |
not assigned |
openURL |
url_ver=Z39.88-2004&ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fvufind.svn.sourceforge.net%3Agenerator&rft.title=Cytotoxic+synergy+between+the+multikinase+inhibitor+sorafenib+and+the+proteasome+inhibitor+bortezomib+in+vitro%3A+induction+of+apoptosis+through+Akt+and+c-Jun+NH2-terminal+kinase+pathways&rft.date=2006-09-01&genre=article&issn=1538-8514&volume=5&issue=9&spage=2378&epage=2387&pages=2378-2387&jtitle=Molecular+Cancer+Therapeutics&atitle=Cytotoxic+synergy+between+the+multikinase+inhibitor+sorafenib+and+the+proteasome+inhibitor+bortezomib+%3Ci%3Ein+vitro%3C%2Fi%3E%3A+induction+of+apoptosis+through+Akt+and+c-Jun+NH2-terminal+kinase+pathways&aulast=Adjei&aufirst=Alex+A.&rft_id=info%3Adoi%2F10.1158%2F1535-7163.mct-06-0235&rft.language%5B0%5D=eng |
SOLR | |
_version_ | 1792338352864755720 |
author | Yu, Chunrong, Friday, Bret B., Lai, Jin-Ping, Yang, Lin, Sarkaria, Jann, Kay, Neil E., Carter, Christopher A., Roberts, Lewis R., Kaufmann, Scott H., Adjei, Alex A. |
author_facet | Yu, Chunrong, Friday, Bret B., Lai, Jin-Ping, Yang, Lin, Sarkaria, Jann, Kay, Neil E., Carter, Christopher A., Roberts, Lewis R., Kaufmann, Scott H., Adjei, Alex A., Yu, Chunrong, Friday, Bret B., Lai, Jin-Ping, Yang, Lin, Sarkaria, Jann, Kay, Neil E., Carter, Christopher A., Roberts, Lewis R., Kaufmann, Scott H., Adjei, Alex A. |
author_sort | yu, chunrong |
container_issue | 9 |
container_start_page | 2378 |
container_title | Molecular Cancer Therapeutics |
container_volume | 5 |
description | <jats:title>Abstract</jats:title> <jats:p>This study was undertaken to characterize preclinical cytotoxic interactions for human malignancies between the multikinase inhibitor sorafenib (BAY 43-9006) and proteasome inhibitors bortezomib or MG132. Multiple tumor cell lines of varying histiotypes, including A549 (lung adenocarcinoma), 786-O (renal cell carcinoma), HeLa (cervical carcinoma), MDA-MB-231 (breast), K562 (chronic myelogenous leukemia), Jurkat (acute T-cell leukemia), MEC-2 (B-chronic lymphocytic leukemia), and U251 and D37 (glioma), as well as cells derived from primary human glioma tumors that are likely a more clinically relevant model were treated with sorafenib or bortezomib alone or in combination. Sorafenib and bortezomib synergistically induced a marked increase in mitochondrial injury and apoptosis, reflected by cytochrome c release, caspase-3 cleavage, and poly(ADP-ribose) polymerase degradation in a broad range of solid tumor and leukemia cell lines. These findings were accompanied by several biochemical changes, including decreased phosphorylation of vascular endothelial growth factor receptor-2, platelet-derived growth factor receptor-β, and Akt and increased phosphorylation of stress-related c-Jun NH2-terminal kinase (JNK). Inhibition of Akt was required for synergism, as a constitutively active Akt protected cells against apoptosis induced by the combination. Alternatively, the JNK inhibitor SP600125 could also protect cells from apoptosis induced by the combination, indicating that both inhibition of Akt and activation of JNK were required for the synergism. These findings show that sorafenib interacts synergistically with bortezomib to induce apoptosis in a broad spectrum of neoplastic cell lines and show an important role for the Akt and JNK pathways in mediating synergism. Further clinical development of this combination seems warranted. [Mol Cancer Ther 2006;5(9):2378–87]</jats:p> |
doi_str_mv | 10.1158/1535-7163.mct-06-0235 |
facet_avail | Online, Free |
finc_class_facet | Medizin |
format | ElectronicArticle |
format_de105 | Article, E-Article |
format_de14 | Article, E-Article |
format_de15 | Article, E-Article |
format_de520 | Article, E-Article |
format_de540 | Article, E-Article |
format_dech1 | Article, E-Article |
format_ded117 | Article, E-Article |
format_degla1 | E-Article |
format_del152 | Buch |
format_del189 | Article, E-Article |
format_dezi4 | Article |
format_dezwi2 | Article, E-Article |
format_finc | Article, E-Article |
format_nrw | Article, E-Article |
geogr_code | not assigned |
geogr_code_person | not assigned |
id | ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTE1OC8xNTM1LTcxNjMubWN0LTA2LTAyMzU |
imprint | American Association for Cancer Research (AACR), 2006 |
imprint_str_mv | American Association for Cancer Research (AACR), 2006 |
institution | DE-Zi4, DE-Gla1, DE-15, DE-Pl11, DE-Rs1, DE-14, DE-105, DE-Ch1, DE-L229, DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161 |
issn | 1535-7163, 1538-8514 |
issn_str_mv | 1535-7163, 1538-8514 |
language | English |
last_indexed | 2024-03-01T15:30:52.835Z |
match_str | yu2006cytotoxicsynergybetweenthemultikinaseinhibitorsorafenibandtheproteasomeinhibitorbortezomibinvitroinductionofapoptosisthroughaktandcjunnh2terminalkinasepathways |
mega_collection | American Association for Cancer Research (AACR) (CrossRef) |
physical | 2378-2387 |
publishDate | 2006 |
publishDateSort | 2006 |
publisher | American Association for Cancer Research (AACR) |
record_format | ai |
recordtype | ai |
series | Molecular Cancer Therapeutics |
source_id | 49 |
spelling | Yu, Chunrong Friday, Bret B. Lai, Jin-Ping Yang, Lin Sarkaria, Jann Kay, Neil E. Carter, Christopher A. Roberts, Lewis R. Kaufmann, Scott H. Adjei, Alex A. 1535-7163 1538-8514 American Association for Cancer Research (AACR) Cancer Research Oncology http://dx.doi.org/10.1158/1535-7163.mct-06-0235 <jats:title>Abstract</jats:title> <jats:p>This study was undertaken to characterize preclinical cytotoxic interactions for human malignancies between the multikinase inhibitor sorafenib (BAY 43-9006) and proteasome inhibitors bortezomib or MG132. Multiple tumor cell lines of varying histiotypes, including A549 (lung adenocarcinoma), 786-O (renal cell carcinoma), HeLa (cervical carcinoma), MDA-MB-231 (breast), K562 (chronic myelogenous leukemia), Jurkat (acute T-cell leukemia), MEC-2 (B-chronic lymphocytic leukemia), and U251 and D37 (glioma), as well as cells derived from primary human glioma tumors that are likely a more clinically relevant model were treated with sorafenib or bortezomib alone or in combination. Sorafenib and bortezomib synergistically induced a marked increase in mitochondrial injury and apoptosis, reflected by cytochrome c release, caspase-3 cleavage, and poly(ADP-ribose) polymerase degradation in a broad range of solid tumor and leukemia cell lines. These findings were accompanied by several biochemical changes, including decreased phosphorylation of vascular endothelial growth factor receptor-2, platelet-derived growth factor receptor-β, and Akt and increased phosphorylation of stress-related c-Jun NH2-terminal kinase (JNK). Inhibition of Akt was required for synergism, as a constitutively active Akt protected cells against apoptosis induced by the combination. Alternatively, the JNK inhibitor SP600125 could also protect cells from apoptosis induced by the combination, indicating that both inhibition of Akt and activation of JNK were required for the synergism. These findings show that sorafenib interacts synergistically with bortezomib to induce apoptosis in a broad spectrum of neoplastic cell lines and show an important role for the Akt and JNK pathways in mediating synergism. Further clinical development of this combination seems warranted. [Mol Cancer Ther 2006;5(9):2378–87]</jats:p> Cytotoxic synergy between the multikinase inhibitor sorafenib and the proteasome inhibitor bortezomib <i>in vitro</i>: induction of apoptosis through Akt and c-Jun NH2-terminal kinase pathways Molecular Cancer Therapeutics |
spellingShingle | Yu, Chunrong, Friday, Bret B., Lai, Jin-Ping, Yang, Lin, Sarkaria, Jann, Kay, Neil E., Carter, Christopher A., Roberts, Lewis R., Kaufmann, Scott H., Adjei, Alex A., Molecular Cancer Therapeutics, Cytotoxic synergy between the multikinase inhibitor sorafenib and the proteasome inhibitor bortezomib in vitro: induction of apoptosis through Akt and c-Jun NH2-terminal kinase pathways, Cancer Research, Oncology |
title | Cytotoxic synergy between the multikinase inhibitor sorafenib and the proteasome inhibitor bortezomib in vitro: induction of apoptosis through Akt and c-Jun NH2-terminal kinase pathways |
title_full | Cytotoxic synergy between the multikinase inhibitor sorafenib and the proteasome inhibitor bortezomib in vitro: induction of apoptosis through Akt and c-Jun NH2-terminal kinase pathways |
title_fullStr | Cytotoxic synergy between the multikinase inhibitor sorafenib and the proteasome inhibitor bortezomib in vitro: induction of apoptosis through Akt and c-Jun NH2-terminal kinase pathways |
title_full_unstemmed | Cytotoxic synergy between the multikinase inhibitor sorafenib and the proteasome inhibitor bortezomib in vitro: induction of apoptosis through Akt and c-Jun NH2-terminal kinase pathways |
title_short | Cytotoxic synergy between the multikinase inhibitor sorafenib and the proteasome inhibitor bortezomib in vitro: induction of apoptosis through Akt and c-Jun NH2-terminal kinase pathways |
title_sort | cytotoxic synergy between the multikinase inhibitor sorafenib and the proteasome inhibitor bortezomib <i>in vitro</i>: induction of apoptosis through akt and c-jun nh2-terminal kinase pathways |
title_unstemmed | Cytotoxic synergy between the multikinase inhibitor sorafenib and the proteasome inhibitor bortezomib in vitro: induction of apoptosis through Akt and c-Jun NH2-terminal kinase pathways |
topic | Cancer Research, Oncology |
url | http://dx.doi.org/10.1158/1535-7163.mct-06-0235 |