We have previously shown that 5’-nitro-indirubinoxime (5’-NIO) has potent anti-tumor effect in various human cancer cells. But the potential anti-invasive effect of 5’-NIO in salivary gland cancer has not been studied yet. The goal of this study is to evaluate the effect of 5'-NIO on salivary gland adenocarcinoma SGT cell adhesion and migration to Type I collagen treatment. Western blot, adhesion and migration assay were performed to evaluate the impacts of 5’-NIO on the expression of MMP-2/-9 and its upstream signaling molecules after treatment of type І collagen. SGT cell adhesion to type I collagen is significantly suppressed by 5’-NIO. 5’-NIO decreased expression of β1 integrin, phosphorylation of FAK, MMP-2/ -9 compared with type I collagen treatment. In addition, 5’-NIO inhibited the migration of SGT cells treated with type I collagen. These results suggest that 5’-NIO could effectively inhibit the invasion and migration of human SGT cells by downregulating the expression of β1 integrin and MMP-2/-9 and phosphorylation of FAK, Akt, and Erk. Adhesion and migration to type I collagen of SGT cells can be influenced through 5’-NIO..

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

A novel indirubin analog, 5'-nitro-indirubinoxime inhibits cell proliferation and induces apoptosis against various human cancer cells. In this study, we performed the microarray analysis to identify genes differentially expressed in the KB oral squamous carcinoma cells after treated with 5'-nitro-indirubinoxime. Among the 10,800 genes analyzed, 1,701 genes (15.8%) showed statistically different expression level in the 5'-nitro-indirubinoxime treated cells with respect to untreated control cells. Among those, 263 genes (15.5%) were down-regulated and 220 genes (12.9%) were up-regulated more than 2-fold. Functionally related gene clusters include genes associated with signal transduction (18.1%), especially genes related with apoptosis (3.5%) and cell cycle regulation (5.8%). Our application of microarray analysis on 5'-nitro-indirubinoxime treated oral cancer cells allows the identification of candidate genes for providing novel insights into the indirubin mediated antitumor activity.

A novel indil‘ubin analog‘ 5’ nitro-indirubinoxime(Ol1) inhibits cell proliferation and induces apoptosis again st variolls hllman cancer cell s. ln this stlldy, we performed the microarray analysis to identify genes diffel'enti ally expressed in the KB oral sqllamollS carcinoma cells after treatment with 011 Of the 10‘ 800 genes a nalyzed , 1700 genes(15.7%) showed di fferent expression level in the 011-treated cells with respect to untreated control cel1s Arnong those‘ 263 genes(15, 5%) were down -reg띠 ated and 220 genes(12, 9%) were IIp-regulated more than 2-fold, Functionally related gene clllsters inclllde genes associated with signal transdllction(18, 1%) , especially genes re lated with a poptosis(3, 5%) and cell cycle reglllation(5. 8%) . Our application of microarray ar뻐ysis on 01l-treated 01'외 cancer cells al lows the identifi cati on of candidate genes for providing novel insights into the 011-mediated anti -tllmor actl Vl ty ,