2'-Hydroxychalcone Induces Autophagy and Apoptosis in Breast Cancer Cells via the Inhibition of the NF-κB Signaling Pathway: In Vitro and In Vivo Studies

2'-Hydroxychalcone is a hydroxyl derivative of Chalcones, which are biosynthetic precursors of Flavonoids and rich in the human diet. The Anticancer activity of 2'-hydroxychalcone has been reported in several cancers but remains to be investigated in breast Cancer. In the current study, 2'-hydroxychalcone showed significant cytotoxicity against breast Cancer cell lines MCF-7 and CMT-1211. It could inhibit breast Cancer cell proliferation, migration, and invasion in vitro and suppress tumor growth and metastasis in vivo. Mechanistic investigation revealed that the NF-κB pathway was significantly inhibited by 2'-hydroxychalcone treatment accompanied by an excessive intracellular accumulation of Reactive Oxygen Species, induction of endoplasmic reticulum stress, and activation of JNK/MAPK. In addition, 2'-hydroxychalcone elevated the autophagic levels in breast Cancer cells equipped with increasing numbers of Autophagy vesicles and complete autophagic flux. Finally, autophagy-dependent Apoptosis was observed in 2'-hydroxychalcone-induced cell death. In conclusion, 2'-hydroxychalcone enhances the autophagic levels and induces Apoptosis in breast Cancer cells, which could be contributed to the inhibition of the pro-survival NF-κB signaling, indicating a promising potential for 2'-hydroxychalcone in future Anticancer drug development.

NF-κB signaling; apoptosis; autophagy; hydroxychalcone; reactive oxygen species.