Abstract
Colorectal cancer is one of the leading causes of death worldwide. Wnt/β-catenin signalling pathway plays a central role in normal cellular responses, making it a potent target in cancer therapy. Study was taken to assess whether ellagic acid modulates Wnt/β-catenin pathway and CDK8 activity in colon cancer cells. Effect of ellagic acid on viability of colon cancer cell lines (HT 29 and HCT 116), were assessed by MTT assay and its influence on CDK8, β-catenin, p-β-catenin, axin1 and 2, survivin, c-Myc and cyclin D1 expressions were determined by western blotting. The levels of survivin, c-Myc and cyclin D1 were also analysed following siCDK8 transfection. Ellagic acid caused significant decrease in viability of HT 29 and HCT 116 cells. Expression of CDK 8, β-catenin, survivin, c-Myc and cyclin D1were markedly reduced on exposure to ellagic acid. Significant up-regulation in the expression of p-β-catenin, axin1 and 2 were observed. siCDK8 transfection resulted in marked reduction in the expression of survivin, c-Myc and cyclin D1. Ellagic acid was able to effectively reduce cell viability and modulate expressions of Wnt/β-catenin signalling cascade proteins and down regulate the activity and expression of CDK8 in HT 29 and HCT 116 cells.
Highlights
Colorectal cancer is the second most frequent malignancy and the second leading cause of death due to cancer globally (Walker et al, 2014)
The present study investigates the effectiveness of ellagic acid in regulating Wnt/ -catenin signaling pathway and in modulating Cyclin-dependent kinase 8 (CDK8) kinase activity in HCT 116 and HT 29 colon cancer cells
The anticancer effect of ellagic acid at 10-50 μM on colon cancer cell lines were assessed by measuring cell viability by MTT assay
Summary
Colorectal cancer is the second most frequent malignancy and the second leading cause of death due to cancer globally (Walker et al, 2014). Cyclin-dependent kinase 8 (CDK8) is implicated in transcriptional regulation of key pathways involved in colon cancers such as Wnt/ -catenin (Kim et al, 2006), Notch (Fryer et al, 2004) and p53 (Donner et al, 2007). The kinase activity of CDK8 is required for regulation of -catenin dependent transcription and oncogenesis (Firestein et al, 2008; Morris et al, 2008). These observations suggest that therapeutic interventions targeting CDK8 and Wnt/ -catenin signaling pathway is of clinical value
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