doi:10.1093/carcin/bgs240
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Ros-Independent Jnk Activation and Multi-Site Phosphorylation of Bcl-2 Link Diallyl Tetrasulfide-Induced Mitotic Arrest to Apoptosis.

       
       
        Kelkel M, Cerella C, Mack F, Schneider T, Jacob C, Schumacher M, Dicato M, Diederich M.
       
        Garlic-derived organosulfur compounds (OSCs) including diallylpolysulfides are well known for various health-beneficial properties and recent reports even point to a potential role of diallylpolysulfides as chemopreventive and -therapeutic agents in cancer treatment due to their selective anti-proliferative effects. In this respect, diallyltri- and -tetrasulfide are reported as strong inducers of an early mitotic arrest and subsequent apoptosis, but the underlying molecular mechanisms and the link between these two events are not yet fully elucidated. Our data revealed that diallyltetrasulfide (DAS4) acts independently of reactive oxygen species (ROS) and tubulin represents one of its major cellular targets. Tubulin depolymerization prevents the formation of normal spindle microtubules thereby leading to G2/M arrest. Here, we provide evidence that JNK, which is activated early in response to DAS4 treatment, mediates multi-site phosphorylation and subsequent proteolysis of the anti-apoptotic protein Bcl-2. As the latter event occurs concomitantly with the onset of apoptosis and the chemical JNK inhibitor SP600125 not only prevented Bcl-2 phosphorylation and proteolysis but also apoptosis following DAS4 treatment, we suggest that these JNK-mediated modulations of Bcl-2 represent the missing link connecting early microtubule inactivation to the induction of apoptosis.
       
       
来源：生物谷