Inhibition of p38 MAPK sensitizes tumour cells to cisplatin‐induced apoptosis mediated by reactive oxygen species and JNK

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The p38 MAPK pathway is an important regulator of many cellular responses. It is well established that p38 MAPK signalling negatively regulates epithelial cell transformation, but enhanced p38 MAPK activity has been also correlated with bad clinical prognosis in some tumour types. Here, we provide genetic and pharmacological evidence showing that p38 MAPK inhibition cooperates with the chemotherapeutic agent cisplatin to kill tumour cells. We show that p38 MAPK inhibition results in ROS upregulation, which in turn activates the JNK pathway via inactivation of phosphatases, sensitizing human tumour cells to cisplatin‐induced apoptosis. Using a mouse model for breast cancer, we confirm that inhibition of p38 MAPK cooperates with cisplatin treatment to reduce tumour size and malignancy in vivo. Taken together, our results illustrate a new function of p38 MAPK that helps tumour cells to survive chemotherapeutic drug treatments, and reveal that the combination of p38 MAPK inhibitors with cisplatin can be potentially exploited for cancer therapy.

Location: Deutsche Nationalbibliothek Frankfurt am Main

Extent: Online-Ressource

Language: Englisch

Bibliographic citation: Inhibition of p38 MAPK sensitizes tumour cells to cisplatin‐induced apoptosis mediated by reactive oxygen species and JNK ; volume:5 ; number:11 ; year:2013 ; pages:1759-1774 ; extent:16
EMBO molecular medicine / European Molecular Biology Organization ; 5, Heft 11 (2013), 1759-1774 (gesamt 16)

Creator: Pereira, Lorena
Igea, Ana
Canovas, Begoña
Dolado, Ignacio
Nebreda, Angel R.

DOI: 10.1002/emmm.201302732

URN: urn:nbn:de:101:1-2023020307212746497989

Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.

Last update: 15.08.2025, 7:28 AM CEST

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Pereira, Lorena
Igea, Ana
Canovas, Begoña
Dolado, Ignacio
Nebreda, Angel R.

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Inhibition of p38 MAPK sensitizes tumour cells to cisplatin‐induced apoptosis mediated by reactive oxygen species and JNK

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Other Objects (12)

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GW501516-activated PPARβ/δ promotes liver fibrosis via p38-JNK MAPK-induced hepatic stellate cell proliferation

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Klonierung, Charakterisierung und Funktion der beiden SAPK-Mitglieder JNK und p38 MAPK des marinen Schwamms S. domuncula

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Klonierung, Charakterisierung und Funktion der beiden SAPK-Mitglieder JNK und p38 MAPK des marinen Schwamms S. domuncula

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