Resistance to temozolomide (TMZ) chemotherapy is the main reason for treatment failure in patients with glioblastoma (GBM). In the present study, we investigated biochanin A (BCA) a potent sensitizer of TMZ in GBM. We observed that BCA significantly enhanced cell sensitivity to TMZ in vitro and in vivo. Mechanistically, the specific chemosensitizing effect of BCA is mediated by autophagy inhibition. Moreover, by performing a molecular docking analysis, we demonstrated that BCA interacts with AMPK residues and impairs autophagy by regulating the AMPK/ULK1 pathway. These results suggest that BCA is a potential therapeutic agent that sensitizes GBM to TMZ and provide new insight into its therapeutic potential in chemoresistant GBM.
Keywords: AMPK; Autophagy; Biochanin A; Chemosensitivity; Glioblastoma; Molecular docking.
© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.