Anti-cancer effects of dopamine in human glioma: involvement of mitochondrial apoptotic and anti-inflammatory pathways

Despite the emergence of innovative cancer treatment strategies, the global burden imposed by malignant glioma is expected to increase; thus, new approaches for treating the disease are urgently required. Dopamine, a monoamine catecholamine neurotransmitter, is currently regarded as an important endogenous regulator of tumor growth. Dopamine may play an important role in glioma treatment; however, the mechanism underlying the anti-tumor activity of dopamine remains poorly understood. Here, we explored the potential roles of dopamine in glioma and highlight the importance of endogenous regulators of tumor growth. We report that dopamine inhibited glioma cell proliferation. We investigated the biological functions of dopamine via migration, colony formation and apoptosis assays in glioma cells. We also evaluated cytochrome c release from the mitochondria and p50 and p65 subcellular localization by fluorescence microscopy. We performed western blotting and real-time quantitative polymerase chain reaction to detect apoptosis and inflammatory marker protein and gene expression levels, respectively. NF-κB p50/p65 nuclear localization was analyzed after U87MG and U251 cells were treated with dopamine. The in vivo anti-tumor efficacy of dopamine was also analyzed in xenograft mice. Taken together, our results indicated that dopamine induced apoptosis by activating the cytochrome c and caspase-dependent apoptotic pathway. Moreover, dopamine markedly down-regulated inflammation-related protein expression levels and p50/p65 NF-κB nuclear localization in tumor cells, thereby inhibiting increases in tumor weight and size in xenograft mice. Thus, therapies targeting the mitochondrial apoptotic and anti-inflammatory signaling pathways regulated by dopamine may represent promising treatments for human glioma.