Inhibition of Rac Induces Hyper-Activation of c-Jun N-Terminal Kinase and Caspase-Dependent Apoptosis / Oral Science International

Apoptosis is one mechanism by which cancer cells can be eliminated. Therefore, understanding the signaling pathways that transduce apoptotic signals in cancer cells is an indispensable component of cancer research. Rac, a member of the Rho family of proteins, has been implicated in the regulation of cell survival and apoptosis. However, the mechanisms underlying this process remain to be elucidated. To understand the role of Rac in oral squamous cancer, we inhibited its activity by a Rac-specific small molecule inhibitor, NSC23766, or transfection of dominant negative Rac (Rac-DN), and discovered that inhibition of Rac activity elicits apoptosis in highly malignant oral squamous carcinoma (OSC-19) cells. Upon suppression of Rac, we observed up-regulation of c-Jun N-terminal kinase (JNK), leading to caspase-dependent apoptosis. Furthermore, stimulation of protein phosphatase (PP5) rescued apoptosis caused by Rac inhibition by dephosphorylating JNK. Taken together, inhibition of Rac activity leads to the suppression of PP5 activity, which results in extensive activation of JNK and caspase-dependent apoptosis. In conclusion, Rac inhibition may represent a novel therapeutic approach for oral squamous carcinoma.

Molecular Analysis of Salivary Gland Branching Morphogenesis / Oral Science International

Recently, clinicians and scientists have focused on tissue engineering for regenerative medical therapy. This approach promises to provide remarkable clinical breakthroughs for the future. In oral and craniofacial medicine, most scientific approaches to tissue engineering currently involve tooth and bone, while little progress has been made toward regenerating organs such as salivary gland. To develop strategies for salivary gland regeneration, it will be important to understand the molecular mechanisms of normal salivary development. This mini-review describes a recently developed and tested set of approaches for identifying and characterizing molecules essential for branching morphogenesis and other developmental processes. It shows the value of using laser microdissection and the new process of T7-SAGE for gene discovery of putative candidate molecules that may be crucial regulators or mediators. We describe a stepwise series of associated strategies for reliable identification and functional testing of a candidate molecule, as well as its successful application to a specific candidate molecule originally identified by T7-SAGE.