Investigation of cytotoxic and genotoxic effects of 5-Fluorouracil combination with dopamine and receptor antagonists in human breast cancer cell line

Dopamine (DA) has many functions in central and peripheral areas. In addition to these functions, recent strong evidences between DA and cancer development have caused this molecule to attract attention in cancer treatment. In this study, the possible cytotoxic and genotoxic effects of DA and dopamine 1 and dopamine 2 receptor (DR1 and DR2) antagonists on human breast cancer cells and the synergistic activity of the compounds with the standard chemotherapy agent 5 Fluorouracil (5-FU) were evaluated. MCF-7 cell line was used in the study. Cells were cultured with Dulbecco's modified eagle medium (DMEM). The effects of the compounds on cell viability levels were determined by colorimetric analyses after 24, 48 and 72 hours of application. Then, combined applications of DA, DR1 and DR2 antagonists and 5-FU were performed considering the determined dose and time period. The effects of single and combined applications of the compounds on DNA damage levels were analyzed by single cell gel electrophoresis. The study results showed that DA and selective DR1 antagonist SCH 23390 (SCH) significantly reduced viability, especially at the 72nd hour, while selective DR2 antagonist L-741,626 (L741) significantly reduced viability at all three time periods. In the combined applications of the relevant compounds with 5-FU, DA and SCH at a dose of 25 µM, and L741 at both doses (10 µM and 25 µM) significantly reduced cell viability compared to 5-FU. According to the DNA damage results, in 1-hour applications, the combinations significantly reduced DNA damage in all parameters compared to 5-FU. However, it was found that this effect decreased significantly in 24-hour applications and no statistically significant synergistic effect was observed. The findings indicate that DA may play a role in increasing the effectiveness of chemotherapy in breast cancer cells. Keywords: Breast cancer, cytotoxicity, dopamine, dopamine receptor antagonist, genotoxicity, L-741,626, SCH-23390, 5-fluorouracil Scientific Field Code: 401.02.00, 401.02.01