Abstract
Female breast cancer has become the most commonly diagnosed cancer worldwide. As a tumor suppressor, estrogen receptor β (ERβ) is a potential target for breast cancer therapy. TAD1822-7 was evaluated for ERβ-mediated autophagy and cell death using cell proliferation assay, Annexin V/PI staining, immunofluorescence, western blotting and hypoxia cell models. TAD1822-7 upregulated ERβ causing cell death and induced mitochondrial dysfunction and autophagy companied with mitochondrial located ERβ. Enhanced levels of LC3-II and p62 indicated that TAD1822-7 blocked the late-stage autolysosome formation, leading to cell death. Mechanistically, TAD1822-7-induced cell death was mediated by PI3K/AKT signaling pathways. Moreover, TAD1822-7 modulated HIF functions and autophagy via the inhibition of HIF-1β in the context of hypoxia-induced autophagy. TAD1822-7 inhibited hypoxia-inducted autophagy and PI3K/AKT pathway. These findings provide new insight into the mechanism underlying the inhibitory effects of TAD1822-7 via ERβ-mediated pathways in breast cancer cells.
Ginkgetin induces cell death in breast cancer cells via downregulation of the estrogen receptor
