Epigallocatechin-3-gallate (EGCG) and theaflavins (TF) are polyphenols included in green and black teas, respectively. Both green and black teas have been studied for their potential health benefits for cancer. Hypoxia-inducible factor (HIF) has been implicated multiple physiological and pathophysiological pathways, particularly, oncogenesis. But, the molecular pathways that govern the cell response to EGCG are not fully elucidated. The present study investigated the intracellular mechanism in oral squamous cell carcinoma (OSCC) cells treated with EGCG, focusing on HIF-1 expression and its effect on epithelial phenotype. EGCG decreased phosphorylated Raf-1 protein in YD 8 OSCC cell, but B-raf protein was not affected at all by EGCG and TF. In addition, we here found that EGCG regulated HIF-1α expression independent of Raf-1 protein. Taken together with our previous result, the result imply that EGCG is attributed to the HIF-1α expression via Raf/MEK/ERK pathway, and the HIF-1α expression is associated with the change of epithelial phenotype in OSCC cell.

Considering the great potential of iron chelators at inhibiting the proliferation of tumor cells, in order to determine the molecular and biological basis for the effects of iron chelator in oral cancer, we investigated the effects of iron chelator, desferrioxamine (DFO), on the gene profiling analysis of immortalized human oral keratinocytes (IHOK), and oral cancer cells (HN12), using the cDNA microarray. We identified 46 clones cDNA exhibiting more than 2 fold overexpression in DFO treated IHOK and HN12 cells, and 94 cDNA reveal more than 2 fold down-regulated expression. Examination of gene expression that differs between DFO treated vs. control IHOK and HN12 cells apprear to be related to : cell cycle regulator, cell growth and apoptosis, signal transduction and stress. p21 for cell cell cycle factor was upregualted, and cyclin-cdk gene was decreased expression, so we observed cell cycle arrest in DFO treated IHOK and HN12 cells. In tumor growth, we have identified downregulation of hemidesmosomal protein (bullous pemphigoid antigen 1) and epiregulin expression in DFO treated IHOK and oral cancer cells. Signal transducers including mitogen-activated protein kinase-activated protein kinase 5, serine/thereonine kinase 6 were downregulated with DFO treated cells, suggesting the DFO regulates the p38 MAP kianse pathway in immortalized and maignant oral keratincytes. In conclusion, we have demonstrated the high-throughput utility of cDNA array hybridization in parallel to the gene expression analysis to identify genes that are expressed differentially in DFO treated with immortalized and malignant oral keratinocytes. The differentially expressed genes identified here should be informative in DFO-induced anti-cancer effects.

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.