Phenylethyl isothiocyanate induces apoptotic signaling via suppressing phosphatase activity against c-Jun N-terminal kinase
| Autor: | Yi-Rong Chen, Tse-Hua Tan, Rajashree Kori, A.-N. Tony Kong, Jin Han |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
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 |
| Zdroj: | The Journal of biological chemistry. 277(42) |
| ISSN: | 0021-9258 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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