A Dendrobium chrysotoxum extract erianin induce AML cells death by activating PPARɑ and downregulating PI3K/AKT signaling pathways

Abstract

Erianin is a biphenyl compound with low toxicity and a single structure that is extracted from Dendrobium officinale. The wide spectrum of pharmacological properties and excellent toxicity of erianin have been comprehensively proven in multiple tumors. However, less is known about the toxicity of erianin in acute myeloid leukemia (acute myeloid leukemia AML). Here, we explored the anti-AML capacity and potential mechanisms of erianin. Cells proliferation and cytotoxicity of AML cells of erianin was detected by CCK-8 assay and flow cytometer was conducted to assess AML cells apoptosis rate. Erianin blocked the AML cells cycle at the G2/M phase by regulating cell cycle-related protein and P21, P27, and P53 mRNA expression. Additionally, we first filtered PPARɑ and PIK3R1 through network pharmacology, protein–protein interaction (PPI) network, and GO and KEGG pathway enrichment analysis and confirmed their binding with erianin by molecular docking analysis.The cellular thermal shift assay (CETSA) and the drug affinity responsive target stability assay (DARTS) further verified that PPARɑ was an effective target of erianin. Specifically, erianin was found to inhibit the transcriptional level of PIK3R1 by promoting the protein expression of PPARɑ, thereby inhibiting the PI3K/AKT pathway. The inhibitory effect of erianin was partially neutralized by GW6471, a PPARɑ inhibitor. Notably, erianin revealed vigoroso coordinate repression with LY294002 on AML cells. Our findings indicate that erianin showed a potent cytotoxic effect on AML cells and affected AML cells via PPARɑ to regulate PI3K/AKT signaling pathways. We demonstrated the potent anti-AML effects of erianin and reported its potential mechanisms of action, indicating its potential for further development as a novel anti-AML drug.