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Phenylethyl isothiocyanate induces apoptotic signaling via suppressing phosphatase activity against c-Jun N-terminal kinase
- Source :
- The Journal of biological chemistry. 277(42)
- Publication Year :
- 2002
-
Abstract
- Dietary isothiocyanates induce apoptosis in various cancer cell lines through a c-Jun N-terminal kinase (JNK)-dependent mechanism. We found that phenylethyl isothiocyanate (PEITC) was capable of inducing JNK activation and apoptosis in prostate cancer cell lines with distinct p53 statuses. PEITC induced JNK-mediated apoptotic signaling via a different pathway than that used by DNA-damaging agents, because genotoxicresistant LNCaP prostate cancer cells were equally sensitive to PEITC as parental LNCaP cells. PEITC did not induce significant MKK4 or MKK7 activation and did not activate JNK directly, suggesting that JNK and JNK upstream kinases are not primary targets of PEITC. The JNK dephosphorylation and inactivation rates were decreased in cells exposed to PEITC. Expression levels of M3/6, a JNK-specific phosphatase, were down-regulated by PEITC via a proteasome-dependent mechanism. Taken together, our data suggest that PEITC activates JNK through suppression of JNK dephosphorylation and that PEITC may be an alternative therapeutic agent for cancers that are resistant to genotoxic agents. This study also reveals that JNK phosphatases are potential targets for the development of novel cancer therapeutic agents.
- Subjects :
- Male
Phenethyl isothiocyanate
Time Factors
Phosphatase
Blotting, Western
Down-Regulation
Apoptosis
DNA Fragmentation
Transfection
Biochemistry
Dephosphorylation
chemistry.chemical_compound
Adenosine Triphosphate
Isothiocyanates
LNCaP
medicine
Tumor Cells, Cultured
Humans
Phosphorylation
Molecular Biology
Dose-Response Relationship, Drug
Chemistry
Kinase
c-jun
JNK Mitogen-Activated Protein Kinases
Cancer
Prostatic Neoplasms
Dose-Response Relationship, Radiation
Cell Biology
medicine.disease
Precipitin Tests
Phosphoric Monoester Hydrolases
Cell biology
Mitogen-Activated Protein Kinases
Tumor Suppressor Protein p53
Plasmids
Propidium
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 277
- Issue :
- 42
- Database :
- OpenAIRE
- Journal :
- The Journal of biological chemistry
- Accession number :
- edsair.doi.dedup.....c46ac47092f8c1c76d9946ea2d0599dc