Effects of platinum-coexisting dopamine with X-ray irradiation upon human glioblastoma cell proliferation

AbstractIn brain tumors, neurotransmitters and platinum drugs may have some interaction, but their role in radiation therapy remains unclear. We investigated the effects of dopamine in combination with platinum on human glioblastoma U-251MG cells upon X-ray irradiation, comparing withl-DOPA, 2-phenylethylamine and temozolomide. Cell proliferation of U-251MG cells was prominently decreased by dopamine in combination with 10  μM platinum upon 4 Gy of X-ray irradiation, accompanied with intracellular reactive oxygen species generation and mitotic catastrophe. Platinum alone did not increase intracellular reactive oxygen species. On the other hand,l-DOPA in combination with platinum did not decrease cell proliferation regardless of X-ray irradiation. It was clearly shown that 2-phenylethylamine did not suppress cell proliferation as compared to dopamine. Temozolomide decreased cell proliferation in a dose-dependent manner upon X-ray irradiation. However, the combined administration of temozolomide and platinum did not further decrease cell proliferation. The platinum nanoparticles were gradually taken up by cells after administration as determined by ICP analysis. Our results suggest that platinum-coexisting dopamine led cells to mitotic catastrophe due to increased production of intracellular reactive oxygen species which was boosted by X-ray and platinum-catalyzed auto-oxidation of dopamine, and thereby cell proliferation was suppressed. In addition, normal human fibroblast ...
Source: Human Cell - Category: Cytology Source Type: research