Functional Evaluation of Imatinib mesylate in Hepatocellular Carcinoma Cells
Mai A. Saad Zaghloul, Ashraf H. Abadi and Ahmed I. Abdelaziz
Pages 65-71 (7)
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.
Hepatocellular carcinoma, HuH-7, imatinib mesylate, luciferase reporter gene, molecular targeted therapy, p53, MAPK, Gastrointestinal Tumors, Functional Integrity Assay
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.