Ginseng polysaccharide inhibits MDA-MB-231 cell proliferation by activating the inflammatory response.

Abstract

Ginseng polysaccharide (GPS) is known for its efficacy in cancer therapy; however, its regulatory mechanism in breast cancer (BC) remains unclear. To analyze the effect of GPS on BC cell proliferation, cell proliferation rate calculations, western blotting, plasmid transfections, electrophoretic mobility shift assays and chromatin immunoprecipitation assays were performed. GPS treatment in the culture cell medium inhibited cell proliferation in the BC cell line MDA-MB-231. In addition, the E-cadherin level was enhanced while the vimentin level was suppressed following GPS treatment (both P<0.05). Furthermore, the levels of apoptotic markers, including cleaved-Caspase-3 and p53, and inflammatory response markers, including plasminogen activator inhibitor and TNF-α, were induced by GPS treatment in MDA-MB-231 cells (all P<0.05). These results indicated that GPS supplementation activated the inflammatory response and apoptosis in BC cells. GPS treatment activated the phosphorylation levels of c-Jun N-terminal kinase, Akt and NF-κB. In MDA-MB-231 cells, GPS resulted in the accumulation of the NF-κB components p65, p50 and Ikaros family zing finger protein 1 (IKZF1; all, P<0.05). Chromatin immunoprecipitation and electrophoretic mobility shift assays indicated that p65 bound to the IKZF1 promoter. The overexpression of IKZF1 or p65 inhibited MDA-MB-231 cell proliferation (P<0.05), indicating that GPS treatment may inhibit BC cell proliferation by the activation of IKZF1. Taken together, these results suggested that GPS significantly inhibited BC cell proliferation via the control of the biological processes, including the activation of p65-IKZF1 signaling and apoptosis. The data indicated a novel mechanism for further understanding of cancer cell proliferation.