Inhibition of perillyl alcohol on cell invasion and migration depends on the Notch signaling pathway in hepatoma cells

Cell metastasis, especially the process of invasion and migration, is considered as the main cause for the high mortality rate of hepatocellular carcinoma (HCC), which has become the sixth most common cancer worldwide and the third leading cause of cancer death. In this present study, we aimed to exploit the effects of perillyl alcohol on cell invasion and migration and the underlying molecular mechanisms in HCC. According to the transwell assays, cell invasiveness and migratory capacity were markedly higher in hepatoma cells (HepG2, SMMC-7721 and MHCC97H) than those in normal liver cells (HL-7702), and then significantly suppressed by perillyl alcohol treatment ( P < 0.05). Meanwhile, the mRNA levels of Notch signaling pathway downstream target genes, HES1 , HES5 , and HEY1 , were notably higher in hepatoma cells detected with real-time reverse transcription polymerase chain reaction (RT-PCR) ( P < 0.05). After treated with perillyl alcohol, these mRNA levels were significantly decreased in hepatoma cells ( P < 0.05). In addition, compared with the normal liver cells, the protein expression levels of Notch1 intracellular domain (N1ICD) and Snail were significantly increased, while E-cadherin protein expression was significantly decreased in hepatoma cells ( P < 0.05). However, perillyl alcohol treatment significantly decreased N1ICD and Snail protein expressions and increased E-cadherin protein expression in hepatoma cells ( P < 0.05). In conclusion, perillyl alcohol might play an important role in the process of hepatoma cell invasion and migration via decreasing the activity of Notch signaling pathway and increasing E-cadherin expression regulated by Snail.