Erianin suppresses the development of acute myeloid leukemia via PPARɑ and regulating PI3K/AKT signaling pathways

Acute myelogenous leukemia is a highly invasiveness hematological malignancies that mainly relies on chemotherapy to improve survival rate at present.Up to now,the application of natural products has been widely accepted as an alternative compared with conventional chemotherapeutic agents due to their relative safety.In our research,we attempted to explore the anti-AML capacity and the potential mechanism of Erianin(Eri), a natural component from Chinese herbal medicine Dendrobium flaviflorum.We verified that Erianin inhibited the proliferation of AML cells and induced their apoptosis.Erianin can block cell cycle of AML cells at G2/M phase thourgh regulation of cell cycle-related proteins and P21,P27,P53 mRNA expression.Mechanistically, we firstly filtered and locked PPARɑ and PIK3R1 through network pharmacology analysis, protein-protein interaction (PPI) network, GO and KEGG pathway enrichment analysis, and further confirmed their good binding with Erianin by molecular docking.Specifically,Erianin inhibited the transcriptional level of PIK3R1 by activating the protein level of PPARɑ, thereby inhibiting the PI3K/AKT pathway.The inhibitory ability of Erianin on AML cells was partially neutralized by GW6471,an inhibitor of PPARɑ.It was also worth noting that Erianin revealed vigoroso coordinate repression with LY294002 on AML cells. Overall, these evidences indicated that Erianin exerted an influence on AML cells at least partially through PPARɑ to regulate PI3K/AKT signaling pathways.In summarize, we demonstrated the potent anti-AML effect and the potential mechanisms of Erianin, which suggested a hopeful strategy that Erianin has the capacity to be developed into a novel anti-AML drug.