TPD7 inhibits the growth of cutaneous T cell lymphoma H9 cell through regulating IL‐2R signalling pathway

Abstract

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.

ND‑09 inhibits chronic myeloid leukemia K562 cell growth by regulating BCR‑ABL signaling

“…Findings have shown that BCR-ABL exerts anti-apoptotic effects that play an important role in the development of CML (20). Furthermore, the intrinsic mitochondrial pathway is one of the two main apoptotic pathways (21). In the current study, ND-09 was found to induce apoptosis in K562 cells, an effect that was relatively higher in K562 cells than in JURKAT and HUT78 cells (Fig.…”

Janus Kinase Signaling: Oncogenic Criminal of Lymphoid Cancers

“…Besides, a vitamin A derivative, 9-cis-RA, induced CTCL cellular apoptosis dose-and time-dependently via decreasing JAK1/STAT3/STAT5 phosphorylation, Bcl-xL and cyclin D1 levels [114]. A novel taspine derivate TPD7 was able to bind to the IL-2 receptor in CTCL and therefore suppressed the downstream cascade, including JAK/STAT and PI3K/AKT/mTOR [115] Additionally, another compound ONC201 exerted time-dependent cell survival inhibition in CTCL cell lines and patient-derived primary CD4+ malignant T cells, and the JAK/STAT pathway was downregulated with ONC201 treatment [116]. These derivatives or inhibitors demonstrated effectiveness and selectivity in harnessing JAK/STAT in order to treat CTCL.…”