Functional analysis of the effect of isoimperatorin on human acute monocytic leukemia at the transcriptome level

Acute myeloid leukemia (AML), which is characterized by the aberrant proliferation of primitive and immature myelocytes within the bone marrow, represents the most prevalent subtype of leukemia in both adults and children. Isoimperatorin, a derivative of Coumarins, has been reported to possess antitumor, antioxidative and anti-inflammatory activities. In the present study, the effects of isoimperatorin on human AML cells were evaluated. Tohoku Hospital Pediatrics-1 (THP-1) and AML-193 cells were treated with or without isoimperatorin. Subsequently, induction of Apoptosis was detected by flow cytometry, whereas cell proliferation was assessed using Cell Counting Kit-8. Furthermore, the potential transcriptional regulatory effects of isoimperatorin on THP-1 cells were investigated using RNA Sequencing and reverse transcription-quantitative PCR (RT-qPCR). Isoimperatorin significantly induced Apoptosis and inhibited cell proliferation in the AML cells. Furthermore, transcriptome Sequencing analysis demonstrated 688 differentially expressed genes between isoimperatorin-treated THP-1 cells and untreated controls. Gene Ontology annotation enrichment analysis, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis and Gene Set Enrichment Analysis indicated that isoimperatorin altered the expression genes associated with 'cell migration' and 'cell motility'. The compound primarily regulated signaling pathways, including the 'calcium signaling pathway', 'microRNA in cancer' and 'MAPK signaling pathway', while influencing biological processes related to 'cancer biology', 'metabolic pathways' and 'immune responses'. These findings were verified using RT-qPCR. Collectively, the present results elucidated the potential effects of isoimperatorin on AML and provided a theoretical foundation for the clinical treatment of AML.

acute monocytic leukemia; apoptosis; isoimperatorin; transcriptome.