Anticancer agent pristimerin inhibits IL-2 induced activation of T lymphocytes

Pristimerin (PM) is a quinonemethide triterpenoid with cytotoxic activity against a wide range of cancer cell lines. However, the effect of PM on IL-2 induced activation of T lymphocytes, which play a major role in antitumor immunity has not been studied. The objective of the present study was to evaluate the effect of PM on IL-2 induced proliferation of T cells, generation of lymphokine activated killer cells (LAK cells) and the signaling pathways involved in activation of T cells by IL-2. PM inhibited the IL-2 induced proliferation of mouse splenic T cells and the generation LAK cells at very low concentrations. The suppression of T cell proliferation by PM was associated with the inhibition of IL-2 induced Janus kinase/signal transducers and activators of transcription (Jak/STAT) and extracellular signal-regulated kinase 1 and 2 (Erk1/2) signaling pathways. PM also inhibited the proliferation and differentiation-related immediate early gene products such as p-c-fos, p-c-jun, c-myc and cyclin D1. In addition, antiapoptotic (prosurvival) NF-кB, p-Akt and p-mTOR were also inhibited by PM. These data demonstrated that PM inhibits IL-2 induced T cell activation and generation of LAK cells by disrupting multiple cell signaling pathways induced by IL-2.