Non-specific anti-proliferative effect of FTY720, a derivative of fungal metabolite from Iscaria sinclarii

Abstract

FTY720 is a derivative of ISP-1 (myriocin), a fungal metabolite of the Chinese herb Iscaria sinclarii, with agonistic effect for sphingosine-1-phosphate receptor. In this study, we examined the potential adverse effect of FTY720 in terms of cell cytotoxicity and the relevance to its pharmacological action, using cell proliferation assay and functional aspect of activated macrophages producing NO and TNF-alpha. FTY720 potently blocked the proliferation of allogeneic T cells. However, this compound did not strongly suppress Con A-induced T cell blastogenesis and IL-2 induced CTLL-2 cell proliferation. Furthermore, FTY720 also non-specifically blocked the proliferation or viability of cancerous or primary cells tested, indicating its potential adverse effects. Interestingly, however, the non-specific inhibitory feature of FTY720 seems not to alter its pharmacological action, according to regulatory role of FTY720 on the production of TNF-alpha and NO from LPS-activated RAW264.7 cells, regardless of serum level. Therefore, our results suggest that FTY720 might have additional non-specific anti-proliferative activity, distinct from its pharmacological activity.