Curcumin induces the differentiation of myeloid-derived suppressor cells and inhibits their interaction with cancer cells and related tumor growth
Menée in vitro et à l'aide d'une xénogreffe de cancer gastrique humain et d'une allogreffe murine de cancer du côlon, cette étude montre que la curcumine, une épice extraite de la plante herbacée "Curcuma longa", induit la différenciation des cellules myéloïdes suppressives et inhibe leur interaction avec les cellules tumorales
Myeloid-derived suppressor cells (MDSCs) accumulate in the spleen and tumors and contribute to tumor growth, angiogenesis and progression. In this study, we examined the effects of curcumin on the activation and differentiation of MDSCs, their interaction with human cancer cells and related tumor growth. Treatment with curcumin in the diet or by i.p. injection significantly inhibited tumorigenecity and tumor growth, decreased the percentages of MDSCs in the spleen, blood and tumor tissues, reduced IL-6 levels in the serum and tumor tissues in a human gastric cancer xenograft model and a mouse colon cancer allograft model. Curcumin treatment significantly inhibited cell proliferation and colony formation of cancer cells and decreased the secretion of murine interleukin (IL)-6 by MDSCs in a co-culture system. Curcumin treatment inhibited the expansion of MDSCs, the activation of Stat3 and NF-kB in MDSCs, and the secretion of IL-6 by MDSCs when MDSCs were cultured in the presence of IL-1beta, or with cancer cell- or myofibroblast-conditioned medium. Furthermore, curcumin treatment polarized MDSCs toward a M1-like phenotype with an increased expression of CCR7 and decreased expression of dectin 1 in vivo and in vitro. Our results demonstrate that curcumin inhibits the accumulation of MDSCs and their interaction with cancer cells and induces the differentiation of MDSCs. The induction of MDSC differentiation and inhibition of the interaction of MDSCs with cancer cells are potential strategies for cancer prevention and therapy.