Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer and the identification of novel therapeutic strategies is required. Mitochondrial dynamic processes have emerged as key processes in the maintenance of liver mitochondrial homeostasis. In addition, some data are accumulating on the role played by mitochondrial dynamics during cancer development. Rotenone is a toxicant that specifically inhibits the flow of electrons through the mitochondrial respiratory chain by binding with mitochondrial complex-I. It has been suggested mitochondria-mediated apoptosis and reactive oxygen species induced by rotenone in liver. Present investigation was aimed to study the effect of rotenone on mff and mid49 (mief2) genes expression, two actors involved in mitochondrial dynamics, in human hepatocellular carcinoma cells (HepG2). At the first part of the study the effect of rotenone toxicity on cell growth of HepG2 cells using MTT method was evaluated. Quantitative study of mff and mief2 gene expression was performed by Real-time PCR. The data obtained for IC50 values showed a significant decrease (50%) in the number of viable cells at concentrations of 2.5- and 5-μM of rotenone for 24 and 48 hours. The results of qPCR showed that a significant decrease (P = 0.018) of mff gene expression in presence of 5μM rotenone. Data obtained from mief2 gene expression showed that there was evidence (p < 0.001) of a difference between the control and the group that they receive 2.5μM rotenone. In this study, we investigated for the first time, the effect of rotenone on relative gene expression level of the genes involved in mitochondrial dynamic. Our results indicted the mRNA level of mff and mief2 genes was altered in response of toxicity effect of rotenone. These results can be explained by altered balance between mitochondrial fusion and fission in HepG2 tumor cells due to apoptotic effect of rotenone.
