Presentation: 2025 ND EPSCoR Annual conference 

October 21, 2025, NDSU Memorial Union, Fargo, North Dakota

Melatonin Exposure Causes an Additive Effect with Doxorubicin in DU-145 and PC3 Prostate Cancer Cell Lines

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. Melatonin has been shown to increase E-cadherin expression in MCF7 breast cancer cells. The hypothesis is that increase in E-cadherin expression leads to a more epithelial-like phenotype, which may make cells more sensitive to traditional cytostatic drugs. In this study, cells exposed to melatonin were exposed to doxorubicin to see the effect of melatonin on doxorubicin toxicity in prostate cancer cell lines. DU-145 and PC3 (prostate cancer cells) were exposed continuously to melatonin for 4 weeks at 0nM, 3nM, and 3µM. After 1, 2, 3, and 4 weeks of exposure, cells were split and prepared for immunofluorescence staining, western blotting, and the synergy experiment. For the synergy experiment, DU-145 and PC3 cells were exposed to melatonin at 0nM, 3 nM and 3 uM in combination with doxorubicin (0-2.5uM), a chemotherapy drug, to see if melatonin increased the sensitivity of cells to doxorubicin by an additive or synergistic effect. Increase in E-cadherin expression was determined by immunofluorescent staining and western blotting. Results show that melatonin had an additive effect on doxorubicin toxicity. Additional experiments performed in the VCSU lab showed a lack of toxicity due to melatonin exposure making a synergistic effect unlikely.