Molecular Mechanisms of c-Jun N-terminal Kinase-mediated Apoptosis Induced by Anticarcinogenic Isothiocyanates

• DOI: 10.1074/jbc.273.3.1769
• Publication Date: 2002-07-26T14:47:21Z
• Authors: Yi-Rong Chen; Wenfu Wang; A.-N. Tony Kong; Tse-Hua Tan
• Keywords: Phenethyl isothiocyanate; c-jun

Isothiocyanates have strong chemopreventive properties against many carcinogen-induced cancers in experimental animal models. Here, we report that phenylmethyl isocyacyanate (PMITC) and phenylethyl isothio- cyanate (PEITC) induced sustained c-Jun N-terminal kinase (JNK) activation a dose-dependent manner. The JNK caused by isothiocyanates was associated with apoptosis induction various cell types. An inhibitor of the caspase/interleukin-1β-converting enzyme blocked isothiocyanate-induced without inhibiting activation, which suggests is an event independent or upstream proteases. PEITC-induced suppressed interfering pathway dominant-negative mutant JNK1 MEKK1 (JNK1(APF) MEKK1(KR), respectively), implying required for apoptotic signaling. Isothiocyanate-induced antioxidants 2-mercaptoethanol and<i>N</i>-acetyl-l-cysteine, suggesting death signaling triggered oxidative stress. Overexpression Bcl-2 activation. In addition, Bcl-x_L apoptosis, but failed to protect cells from overexpression activated JNK1. These results suggest are JNK. Taken together, our indicate (i) mediates PMITC- (ii) PMITC PEITC may chemotherapeutic functions besides their functions.