Dopamine-Induced Lymphoma Cell Death by Inhibition of Hormone Release

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Abstract
Dopamine inhibits prolactin release from pituitary cells and seems to affect the release of several other hormones as well. We report here that dopamine may have similar effects on human B lymphoma cells leading to inhibition of production or release of endogenous factors required for cell viability and proliferation. Thus, addition of dopamine to serum-free cultures of Burkitt lymphoma cells (Raji, Namalwa, Daudi and Jijoye) resulted in rapid and extensive cell death while a myeloma cell line, SKO, appeared to be refractory to this treatment. The addition of FCS or supernatant from serum-free cultures of Raji or T24 bladder carcinoma cells could, to a variable degree, counteract the effect of dopamine, suggesting that dopamine acts by inhibiting the production of essential autocrine factors. When two of the hormones known to be under dopamine control, i.e. prolactin (PRL) and thyrotropin (TSH), were tested, they were able to prevent dopamine-induced cell death if combined with heparin. We further observed that the reducing agent 2-mercaptoethanol (2-ME), which is known to inhibit the binding of TSH to its receptor, displayed similar effects to those of dopamine and was strongly inhibitory for Burkitt lymphoma but not for myeloma cells. As expected from its blocking activity at the receptor level, the effect of 2-ME could not be reversed by adding exogenous factors. Contrary to its effect on B lymphoma cells, 2-ME is essential for growth of the murine T-cell lymphoma line CTLL. However, we show here that dopamine can fully compensate for 2-ME, suggesting that TSH or another factor under dopamine control is intimately involved in the regulation of T-cell growth. This study lends further support to the notion of an active interplay between the neuroendocrine and immune systems and emphasizes PRL and TSH as important regulators of lymphoid cell function. It also shows that these hormones may contribute to the autonomous growth pattern of B lymphoma cells and suggests a potential role for dopamine in the treatment of B-cell tumours.