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Recent Patents on Biomarkers
ISSN (Print): 2210-3090
ISSN (Online): 2210-3104
VOLUME: 3
ISSUE: 1
DOI: 10.2174/2210309011303010065









Functional Evaluation of Imatinib mesylate in Hepatocellular Carcinoma Cells

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Author(s): Mai A. Saad Zaghloul, Ashraf H. Abadi and Ahmed I. Abdelaziz
Pages 65-71 (7)
Abstract:
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.
Keywords:
Hepatocellular carcinoma, HuH-7, imatinib mesylate, luciferase reporter gene, molecular targeted therapy, p53, MAPK, Gastrointestinal Tumors, Functional Integrity Assay
Affiliation:
Molecular Pathology Research Group, Department of Pharmacology and Toxicology, Faculty of Pharmacy and Biotechnology, The German University in Cairo (GUC), New Cairo City - Main Entrance Al Tagamoa Al Khames 11835, Cairo, Egypt.