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Cancer Chemotherapy and Pharmacology
Erschienen in: Cancer Chemotherapy and Pharmacology 4/2008

01.09.2008 | Original Article

c-Jun-NH2-terminal kinase potentiates apoptotic cell death in response to carboplatin in B lymphoma cells

verfasst von: Eiko Takada, Kikumi Hata, Junichiro Mizuguchi

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 4/2008

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Abstract

Purpose

Exposure to carboplatin (CBDCA) has been demonstrated to result in apoptotic and/or necrotic cell death, but molecular mechanisms underlying CBDCA-induced apoptosis or necrosis remain largely unclear. Here, we examined whether activation of c-Jun NH2-terminal kinase (JNK) modulates the mode of cell death induced by CBDCA in CD31 B lymphoma cells.

Methods

The mode of cell death (apoptosis versus necrosis) was investigated by flow cytometry using 7-amino-actinomycin D (7-AAD) and annexin-FITC probes. To evaluate the role of JNK1 in CBDCA-induced cell death, CH31 B lymphoma cells overexpressing dominant-negative form of JNK1 (dnJNK1) or constitutively active form of JNK1 (MKK7-JNK1) were established. Intracellular accumulation of superoxide anion (O2 −) was determined by flow cytometry using the fluorescent probe dihydroethidium (DHE).

Results

The CBDCA-induced primary apoptosis and secondary necrosis were abrogated in the dnJNK1-overexpressing CH31 cells, while it was somewhat enhanced in the MKK7-JNK1-overexpressing cells. In contrast, the CBDCA-induced primary necrosis was reduced by MKK7-JNK1, with a concurrent decrease in production of O2 −. The superoxide anion scavenger for butylated hydroxyanisol (BHA) partially reduced the CBDCA-induced O2 − production and necrotic, but not apoptotic, death in both wild type and dnJNK1-overexpressing CH31 cells.

Conclusions

Prolonged activation of JNK1 appears to be involved in CBDCA-induced apoptosis with prevention of necrosis induction, and the induction of necrosis appears to correlate with CBDCA-induced O2 − production, which is partially blocked by co-culture with BHA. These observations provide valuable information for understanding molecular mechanisms underlying CBDCA-induced cell death, and hopefully for the design of novel treatment modalities for patients with tumors.
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Metadaten
Titel
c-Jun-NH2-terminal kinase potentiates apoptotic cell death in response to carboplatin in B lymphoma cells
verfasst von
Eiko Takada
Kikumi Hata
Junichiro Mizuguchi
Publikationsdatum
01.09.2008
Verlag
Springer-Verlag
Erschienen in
Cancer Chemotherapy and Pharmacology / Ausgabe 4/2008
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-007-0638-x

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