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Functional Evaluation of Imatinib mesylate in Hepatocellular Carcinoma Cells

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Hepatocellular Carcinoma remains a major fatal disease that is resistant to most cytotoxic therapeutics owed to the aberrant activation of signalling cascades. Recent patents reveal a new family of drugs that has been studied for molecularly targeting these cascades; multi-kinase inhibitors, are nowadays considered as novel therapeutic approaches. Therefore in this study, we aimed at investigating the impact of Imatinib mesylate, a tyrosine kinase inhibitor, on Human Hepatoma (HuH-7) cellular behavior and specifically its effect on p53 tumor suppressor gene. HuH-7 cells were transfected with a reporter vector containing a specific enhancer element that is activated upon binding to intracellular p53; consequently downstream luciferase reporter gene is activated. Cells were treated with Imatinib and we looked for p53 induction upon drug stimulation. Additionally; viability, metabolism, proliferation and apoptosis were evaluated. Upon Imatinib treatment, p53 expression showed a significant increase represented in increased luminescence. Moreover; a decrease in cellular viability and metabolic activity along with a considerable inhibition of proliferation and a vast increase in Caspase 9 activity were observed when compared to untreated cells. This study suggests that the effects of Imatinib mesylate might be attributable to enhanced active p53 in HuH-7 cells with consequent reduction in cancer progression properties. The article also summarizes some recent relevant patents.
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Keywords: Functional Integrity Assay; Gastrointestinal Tumors; Hepatocellular carcinoma; HuH-7; MAPK; imatinib mesylate; luciferase reporter gene; molecular targeted therapy; p53

Document Type: Research Article

Publication date: January 1, 2013

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  • Recent Patents on Biomarkers publishes review and research articles, and guest edited thematic issues on important recent patents on biomarkers. The coverage includes novel biomarkers in basic, medical, environmental, and pharmaceutical research. A selection of important and recent patents on biomarkers is also included in the journal. The journal is essential reading for all researchers involved in biomarker research and discovery. The journal also covers recent research (where patents have been registered) in fast emerging patent biomarker applications; discovery and validation are covered for drug discovery, clinical development and molecular diagnostics.
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