Evaluation of Anticancer Effects of Dopamine on Lung Adenocarcinoma Cell Lines
Project no. 22131 · Status: Kapanmış · 2020
Summary
Lung adenocarcinoma originates from alveolar epithelial cells and has a high mortality rate. Dopamine induces apoptosis by p38 in “mitogen activated protein kinase” (MAPK) pathway via dopamine receptor 2 (D2R), which is located on type 2 alveolar epithelial cells. Our hypothesis is that dopamine will reduce the proliferation of lung adenocarcinoma cells, so that we aimed to investigate dopamine’s anticancer effects on the lung adenocarcinoma cell cultures in the present study. We used A549 and NCI-H441 as lung adenocarcinoma cell lines, WI-38 as lung cell lines, dopamine hydrochloride as substance and raclopride tartrate salt as validation of our substance. Control groups were those that received no substance. We performed cytotoxicity assays (Xcelligence RTCA), proliferation assays (CFSE), cell cycle assays, apoptosis assays (Annexin V) and wound healing assays. We did not detect cytotoxicity values for dopamine and raclopride in A549, NCI-H441, and WI-38. 10 µM and 100 µm dopamine concentrations were chosen for A549, NCI-H441 and 79.97 µM for WI-38. 0.1 µM in A549, 88.53 µM in NCI-H441, and 79.97 µM in WI-38 were used as concentrations of raclopride. Dopamine decreased cell proliferation 1.49-fold (100 µm) and 1.61-fold (10 µm) when compared to the control group at 48th hour in A549. We showed no effect of dopamine on cell proliferation of NCI-H441. Dopamine increased cell proliferation 1.75-fold at 24th hour, 1.5-fold at 48th hour in WI-38. There was no effect of raclopride on cell proliferation of A459 and NCI-H441, it suppressed cell proliferation 2-fold in WI-38. We detected no effect of dopamine and raclopride on cell cycles of all of the cell lines, but dopamine and raclopride induced polyploidy 2- and 3-fold, respectively, and their combined polyploidy was induced 5-fold. Apoptotic effects of dopamine were not shown in A549 and NCI-H441, and it increased apoptosis 3.33-fold in WI-38. Raclopride and dopamine induced cell migration. In conclusion, even though dopamine reduces proliferation, the recommendation of its use in the treatment of lung adenocarcinoma is controversial. It should be evaluated in terms of increasing migration and inducing polyploidy. Future in vivo studies investigating the in vitro negative effects of dopamine are needed.