Hinokiflavone induces apoptosis, cell cycle arrest and autophagy in chronic myeloid leukemia cells through MAPK/NF-κB signaling pathway

Background Chronic myeloid leukemia (CML) is a myeloproliferative tumor originating from hematopoietic stem cells, and resistance to tyrosine kinase inhibitors (TKI) has become a major cause of treatment failure. Alternative drug therapy is one of the important ways to overcome TKI resistance. Hinokiflavone (HF) is a C-O-C type biflavonoid with low toxicity and antitumor activity. This study investigated the antitumor effect and possible mechanisms of HF in CML cells. Methods Cell viability was measured by CCK-8 assay. Cell apoptosis and cell cycle distribution were analyzed by flow cytometry. Western blotting was used to assess protein expression levels. Results Our results showed that HF significantly inhibited the viability of K562 cells in a concentration- and time-dependent manner and induced G 2 /M phase arrest by up-regulating p21 and down-regulating Cdc2 protein. Furthermore, HF induced caspase-dependent apoptosis by activating JNK/p38 MAPK signaling pathway and inhibiting NF-κB activity. In addition, HF induced autophagy by increasing LC3-II expression and p62 degradation. Pretreatment with CQ, a late autophagy inhibitor, significantly increased the levels of LC3-II and p62 proteins and promoted cell survival. Conclusion HF shows a good anti-leukemia effect and is expected to become a potential therapeutic drug for CML.

Abstract licence: CC BY-NC-ND

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