Norcantharidin induces cell cycle arrest and inhibits progression of human leukemic Jurkat T cells through mitogen-activated protein kinase-mediated regulation of interleukin-2 production.

摘要

Norcantharidin (NCTD) is a potential anti-cancer agent that inhibits proliferation and induces cell death through regulation of mitogen-activated protein kinases (MAPK). This study examined the effect of NCTD on tumor cells by using a model of phorbol 12-myristate 13-acetate plus ionomycin (PMAI)-activated leukemia Jurkat T cells. The results showed that NCTD significantly inhibited the viability of cells with and without PMAI treatment. NCTD induced cell cycle arrest at G2/M phase, down-regulated the expression of calcineurin and, by itself or in combination with Cyclosporine A, reduced calcineurin phosphatase activity. Furthermore, NCTD up-regulates the expression of phosphorylated (p)-P38 and p-ERK1/2, but not JNK in PMAI-activated Jurkat T cells, in accordance with the alteration in viability. Regarding major cytokine and chemokine secretion profile, NCTD attenuates PMAI-augmented production of IL-2, but slightly increases or has no effect on TNF-alpha and IL-8. By blockade of various MAPK, NCTD regulates PMAI-augmented IL-2 production through activation of P38 and ERK1/2, in accordance with the aforementioned MAPK expression. In conclusion, NCTD inhibited IL-2 production in PMAI-activated human leukemia Jurkat T cells through activation of P38 and ERK1/2, suggesting that NCTD might have the potential of being used as a chemopreventive agent to inhibit tumor progression in the future.