IL-2R pathway is a key regulator in the development of immune cells and has emerged as a promising drug target in cancer treatment, but there is a scarcity of related inhibitors. TPD7 is a novel biphenyl urea taspine derivate, which has been shown anti-cancer effect. Here, we demonstrated the anti-cancer activity of TPD7 in cutaneous T cell lymphoma and investigated the underlying mechanism of TPD7 through IL-2R signalling. The inhibitory effect of TPD7 on cell viability exhibited a strong correlation with the expression level of IL-2R, and cutaneous T cell lymphoma H9 and HUT78 cells were most sensitive to TPD7. TPD7 was nicely bound to IL-2R and down-regulated the mRNA and protein levels of IL-2R. Furthermore, TPD7 suppressed the downstream cascades of IL-2R including JAK/STAT, PI3K/AKT/mTOR and PLCγ/Raf/MAPK signalling, resulting in Bcl-2 mitochondrial apoptosis pathway and cell cycle proteins CDK/Cyclins regulation. And, these were verified by flow cytometry analysis that TPD7 facilitated cell apoptosis in H9 cells via mitochondrial pathway and impeded cell cycle progression at G2/M phase. TPD7 is a novel anti-cancer agent and may be a potential candidate for cutaneous T cell lymphoma treatment by regulating IL-2R signalling pathway.
Keywords: H9; IL-2R; TPD7; cell growth; cutaneous T cell lymphoma.
© 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.