Puerarin sensitized K562/ADR cells by inhibiting NF-κB pathway and inducing autophagy.

Puerarin is an isoflavone isolated from Pueraria lobata (Willd.) Ohwi. In the present study, reversal effect and underlying mechanisms of puerarin on multidrug resistance (MDR) were investigated in K562/ADR cells. K562/ADR cells exhibited adriamycin (ADR) resistance and higher levels of MDR1 expression compared with K562 cells. Puerarin enhanced the chemosensitivity of K562/ADR cells and increased the ADR accumulation in K562/ADR cells. The expression levels of MDR1 were down-regulated by puerarin in K562/ADR cells. Luciferase reporter assay further demonstrated the inhibitory effect of puerarin on TNF-α-induced NF-κB activation. The phosphorylation of IκB-α was significantly suppressed by puerarin. In silico docking analyses suggested that puerarin well matched with the active sites of IκB-α. Moreover, a large number of autophagosomes were found in the cytoplasm of K562/ADR cells after puerarin treatment. The significant increase in LC3-II and beclin-1 was also observed, indicating autophagy induction by puerarin in K562/ADR cells. Puerarin induced cell cycle arrest and apoptosis in K562/ADR cells. Finally, puerarin inhibited phosphorylation of Akt and JNK. In conclusion, puerarin-sensitized K562/ADR cells by downregulating MDR1 expression via inhibition of NF-κB pathway and autophagy induction via Akt inhibition.