Effect of Metformin on the Expression of Cyclin D1 and Mitochondrial COX1 in Squamous Cell Carcinoma Cell Line

Abstract

Most of oral cancers are squamous cell carcinomas representing a major health problem which demands its prevention and treatment. Therefore thorough understanding of the molecular mechanisms involved in the initiation and progression of malignancy is essential to halt the tumor progression. Trials of various chemotherapeutic agents that target molecular genes have been carried out aiming to help improving prognosis in cancer patients and elaborating new forms of treatment. Metformin, is one of the few FDA-approved anti-diabetic drugs owing to its near-perfect safety record, low cost, and favorable side-effect profile, metformin has been recently suggested as a chemo-therapeutic agent owing to its inhibitory and apoptotic effects on cancer cells in many types of cancers, however its action in oral cancers has not been well defined. In the present study we showed the effect of metformin drug in various concentrations 5, 10, and 20mmol for a period of 24, 48, and 72 hours on the viability of cancer cells via MTT assay and also studied its effect on mitochondrial COX-1 and cyclin D1 genes expression in HEp-2 squamous cell carcinoma cell line using real time PCR. Mitochondrial COX-1 is a key factor in aerobic metabolism and is the subunit 1 of complex IV which represents the terminal, energy-transfer enzyme of the respiratory chain, cyclin D1 is a positive regulator of the cell cycle where it binds to complexes that promotes cell cycle progression and thereby cell division, studies have shown that both these two genes are highly expressed in cancer cells.