Indirubin is the ac ti ve ingredi ent of a traditional Chinese herbal medicine, Danggui Longhui Wan, used for t he t reatment of chronic myelocytic leukemia Here, we report that novel indirubin ,- 11‘ ivative‘ 5’ - nitro-indirubinoxime (5’ NIO) , has potent anti- proliferative activity on va rious human cancel‘ cells and oncogenic RK3E- ras rat kidney cells with ha lf- inhibi tory concentrati ons (1C50) ra nging from 1- 12 M, Treatment with indirubin derivative induced the activation 01' caspase 7 rollowed by apoptos is in RK3E- ras cells. lndirubin derivative showed strong anti-tumor activity in rat solid and oral tUll10r models , Direct inj ection of indirubin deri vative every other day for 10 days induced signifi cant inhi bition of tumor growth in Sprague-Dawley rats bearing RK3E- ras-induced tumors Histologically. t reatment with indiru bin de ri vative caused s ignifi cant inhi bit ion of tumor formation with increased apoptosis and decreased tumor cell prolife ration, These f indings provide the potent ial va lue of indirubin deri vative a s a novel candidate for ant i-tumor agents

Indirubin is the active ingredient 0 1' a traditional Chinese herbal medicine, Danggui Longhui Wan, used for the t reatment of chronic myelocytic leu kelma The author reports that novel indirubin derivative, 5'-nitro-indirubinox ime (5'-NIO) , has potent a nti -proliferative activity on human o1'al cancer cells , Treatment of KB cells with 5’ NIO s howed a s t rong cell growth inhibit ion during indicated time point , A typical apoptosis pattern was obtained with DNA fragmenta tion and i mmunofl uorescence analysis of annelxn-v-f!ous Western blot data revealed that p53 and p21CIP1/Waf- l level increased strongJy upon 5'-NIO treatment , The a uthor next tested whether 5'-NIO could activate apoptos is related proteins s uch as caspase-3/-7/-9, [n cells exposed to 5‘-NIO, activation of caspase-3 and -7 was observed, Interesti ngly‘ caspase-9 and cytochrome c cou ld s li ghtly activate in response to 5’-NIO. These results indicate that 5’-NIO strongly induces oral cancer cells apoptosis via a Mi tochondria-mediated cas pase cascade pathway, These observations together s uggest that 5’ NTO may have a possible therapeutic potentia[ to oral cancer

Odontogenic ghost cell tumor (OGCT) is considered as a neoplastic counterpart of the calcifying odontogenic cyst (COC). β-catenin mutations have been described in COC suggesting a critical role in its histogenesis. In this study, we report a patient with OGCT contains a missense mutation on codon 3 (ACT -> TCT). Immunohistochemistry showed nuclear, cytoplasmic, and membranous accumulation of β-catenin in the tumor cells. TUNEL assay showed positive signals in nucleated cells adjacent to the ghost cells. Our data suggest that β-catenin plays an important role in the tumorigenesis of OGCT. OGCT may developed by improper differentiation process coordinated by WNT signaling pathway. Further studies are needed to determine a genotypic/phenotypic characteristics of ghost cell containing odontogenic lesions.