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Anti cancer properties of epigallocatechin 3 gallate EGCG are mediated via apoptosis induction as well as inhibition of cell proliferation and histone deacetylase Accumulation of stabilized cellular FLICE inhibitory protein c FLIP Ku70 complex in the cytoplasm inhibits apoptosis through interruption of extrinsic apoptosis pathway In this study we evaluated the anti cancer role of EGCG in gastric cancer GC cells through dissociation of c FLIP Ku70 complex MKN 45 cells were treated with EGCG or its antagonist MG149 for 24 h Apoptosis was evaluated by flow cytometry and quantitative RT PCR Protein expression of c FLIP and Ku70 was analysed using western blot and immunofluorescence Dissociation of c FLIP Ku70 complex as well as Ku70 translocation were studied by sub cellular fractionation and co immunoprecipitation EGCG induced apoptosis in MKN 45 cells with substantial up regulation of P53 and P21 down regulation of c Myc and Cyclin D1 as well as cell cycle arrest in S and G2 M check points Moreover EGCG treatment suppressed the expression of c FLIP and Ku70 decreased their interaction while increasing the Ku70 nuclear content By dissociating the c FLIP Ku70 complex EGCG could be an alternative component to the conventional HDAC inhibitors in order to induce apoptosis in GC cells Thus its combination with other cancer therapy protocols could result in a better therapeutic outcome

Colorectal cancer (CRC) is the second leading cause of cancer death worldwide that is attributed to gradual long-term accumulation of both genetic and epigenetic changes. To reduce the mortality rate of CRC and to improve treatment efficacy, it will be important to develop accurate noninvasive diagnostic tests for screening, acute and personalized diagnosis. Epigenetic changes such as DNA methylation play an important role in the development and progression of CRC. Over the last decade, a panel of DNA methylation markers has been reported showing a high accuracy and reproducibility in various semi-invasive or noninvasive biosamples. Research to obtain comprehensive panels of markers allowing a highly sensitive and differentiating diagnosis of CRC is ongoing. Moreover, the epigenetic alterations for cancer therapy, as a precision medicine strategy will increase their therapeutic potential over time. Here, we discuss the current state of DNA methylation-based biomarkers and their impact on CRC diagnosis. We emphasize the need to further identify and stratify methylation-biomarkers and to develop robust and effective detection methods that are applicable for a routine clinical setting of CRC diagnostics particularly at the early stage of the disease.

Development is a symphony of cells differentiation in which different signaling pathways are orchestrated at specific times and periods to form mature and functional cells from undifferentiated cells. The similarity of the gene expression profile in malignant and undifferentiated cells is an interesting topic that has been proposed for many years and gave rise to the differentiation-therapy concept, which appears a rational insight and should be reconsidered. Hepatocellular carcinoma (HCC), as the sixth common cancer and the third leading cause of cancer death worldwide, is one of the health-threatening complications in communities where hepatotropic viruses are endemic. Sedentary lifestyle and high intake of calories are other risk factors. HCC is a complex condition in which various dimensions must be addressed, including heterogeneity of cells in the tumor mass, high invasiveness, and underlying diseases that limit the treatment options. Under these restrictions, recognizing, and targeting common signaling pathways during liver development and HCC could expedite to a rational therapeutic approach, reprograming malignant cells to well-differentiated ones in a functional state. Accordingly, in this review, we highlighted the commonalities of signaling pathways in hepatogenesis and hepatocarcinogenesis, and comprised an update on the current status of targeting these pathways in laboratory studies and clinical trials.