Exposure of Melatonin Increases E-cadherin Expression in DU-145 and PC3 Prostate Cancer Cells

E-cadherin plays an essential role in cell-cell connections. Loss of these connections is an important step in the transition of normal cells into cancer cells. The epithelial-mesenchymal transition (EMT) is the transition from a normal cell phenotype to metastatic cells that can grow without restrictions and invade other tissues. Loss of E-cadherin expression is a marker for EMT. Melatonin has been shown to increase E-cadherin expression in MCF7 breast cancer cells. DU-145 cells are metastatic prostate cancer cells that no longer express E-cadherin or in low concentrations. DU-145 cells were exposed to melatonin to see if melatonin can restore and increase E-cadherin expression and, therefore, reverse the EMT process and return the cells to a more epithelial phenotype.
DU-145 and MCF7 were exposed continuously to melatonin for 3 weeks at 3nM, 3µM, and 3mM concentrations. After 7 days, exposed cells were split and prepared for immunofluorescence staining and Western blotting. Melatonin toxicity was determined by MTT assay. Results show that E-cadherin protein levels increased in a time and concentration dependent trend at the 3nM and 3mM concentrations; 3mM proved to be toxic to the cells and caused cell death. In addition, the number of cells that expressed E-cadherin increased, with the greatest expression being found at the intercellular connections. This suggests that functional E-cadherin is present. These results may be significant in treatment by reversing metastatic tumor development. Future experiments will involve patient derived and metastatic breast cancer cell lines. Research is supported by ND-ACES RII Track-I NSF EPSCoR program.