Artesunate attenuates proliferation of epithelial cells by downregulating the NF-κB and AKT signaling pathways in benign mammary gland hyperplasia rats

Background: The aim of this study was to investigate the effects of artesunate (ART) on breast epithelial cell proliferation in vitro and in vivo. Methods: Immortalized human non-cancer mammary epithelial (MCF-10A) cells were used to determine the effect of ART on estrogen-induced mammary hyperplasia cells. We investigated the effect of ART on the synthesis of cyclooxygenase-2 (COX-2) and proliferating cell nuclear antigen (PCNA) in MCF-10A by treating MCF-10A 36 h with different concentrations of ART (0, 100, 200, 400 & micro;m, n=12/group). We then investigated the effect of ART on estrogen induced COX-2, PCNA, nuclear factor-kappa B (NF-xB), and pNF-xB synthesis by treating MCF-10A with both estrogen and ART (0, 50, 100, 200 & micro;m, n=12/group). A mammary hyperplasia model (MGH) was established in rats. All rats (n=12) were divided into 4 groups [group A: negative control (NC) + Art & minus;; group B: NC + Art +; group C: MGH + Art & minus;; group D: MGH + Art +] by the random number table method and the effects of ART on estradiol-induced mammary hyperplasia, fibrosis, and phosphorylation of AKT and NF-xB were studied by histopathological staining, Masson trichrome staining, immunohistochemistry (IHC), and western blotting. Results: The proliferation and inflammation of mammary epithelial cells were blocked by ART (P<0.05). The phosphorylation of NF-xB induced by estradiol in MCF-10A was attenuated by ART (P<0.05). In the rat MGH, ART reduced cell proliferation and fibrosis (P<0.05) and inhibited the phosphorylation of AKT and NF-xB (P<0.05). Conclusions: The drug ART inhibits estrogen-induced breast hyperplasia by blocking AKT and NFkB phosphorylation.

Automated summary

The study showed that artemisinin blocks estrogen-induced breast hyperplasia by inhibiting the phosphorylation of AKT and NFkB, and also reduces cell proliferation and inflammation in mammary epithelial cells.