Inhibition of cell-intrinsic NF-κB activity and metastatic abilities of breast cancer by aloe-emodin and emodic-acid isolated from Asphodelus microcarpus

Anthraquinones are a major class of compounds naturally occurring in Asphodelus microcarpus. The pharmacological actions of anthraquinones in cancer cells are known to induce apoptosis or autophagy, and revert multidrug resistance. In this study, five anthraquinone-type analogs were isolated from the methanol extract of A. microcarpus leaves and identified as, emodin, rhein, physcion, aloe-emodin, and emodic acid. Among them, aloe-emodin and emodic-acid strongly inhibited the proliferation, cells-intrinsic NF-kappa B activity and metastatic ability of breast cancer. Although aloe-emodin inhibited p38 and ERK phosphorylation, emodic-acid more markedly inhibited JNK, in addition to p38 and ERK phosphorylation. Both aloe-emodin and emodic-acid inhibited the secretion of the pro-tumorigenic cytokines IL-1 beta and IL-6, and VEGF and MMP expression, and subsequently inhibited the invasive and migratory potential of 4T1 cells. Thus, our study demonstrated the effects of aloe-emodin and emodin-acid in controlling the migratory and invasive ability of 4T1 breast cancer cells, in addition to inhibiting NF-kappa B activity and the expression of its downstream target molecules.