Curcumin Suppresses Phthalate-induced Metastasis and the Proportion of CSCs-like via the Inhibition of AhR/ERK/SK1 Signaling in Hepatocellular Carcinoma.
J Agric Food Chem. 2015 Nov 20. Epub 2015 Nov 20. PMID: 26585812
Recent evidence indicating that phthalates promote cancer development, including cell proliferation, migration, and invasion, have raised public health concerns. Here, we show that bis(2-ethylhexyl) phthalate promotes the migration, invasion, and epithelial-mesenchymal transition of hepatocellular carcinoma cells. In addition, bis(2-ethylhexyl) phthalate increased the proportion of cancer stem cell (CSC)-like cells and stemness maintenance in vitro as well as tumor growth and metastasis in vivo. The various activities of curcumin, including anti-cancer, anti-inflammation, antioxidation and immunomodulation have been investigated extensively. Curcumin suppressed phthalate-induced cell migration, invasion and epithelial-mesenchymal transition, decreased the proportion of CSC-like cells in hepatocellular carcinoma cell lines in vitro, and inhibited tumor growth and metastasis in vivo. We also revealed that curcumin suppressed phthalate-induced migration, invasion, and CSC-like cells maintenance through inhibition of the aryl hydrocarbon receptor/ERK/SK1/S1P3 signaling pathway. Our results suggest that curcumin may be a potential antidote for phthalate-induced cancer progression.