DataSheet1_Matrine, a potential c-Myc inhibitor, suppresses ribosome biogenesis and nucleotide metabolism in myeloid leukemia.xlsx

Previous studies have shown that matrine, a natural compound extracted from the herb Sophora flavescens, has a good anti-leukemia effect, but its key target and mechanism remains unclear. Here, we found that only c-Myc could respond rapidly to matrine treatment in three myeloid leukemia cell lines, and matrine inhibited both transcription and translation of c-Myc. Ribosome biogenesis and nucleotide metabolism, the key downstream of c-Myc, were significantly suppressed after matrine treatment. Therefore, our results confirmed that matrine is a special c-Myc inhibitor which suppresses ribosome biogenesis and nucleotide metabolism by inhibiting c-Myc in myeloid leukemia. This study provides scientific basis for the development of matrine derivatives to c-Myc-driven cancers.既往研究表明，从苦参（Sophora flavescens）中提取的天然化合物苦参碱（matrine）具备良好的抗白血病活性，但其核心作用靶点与分子机制仍未阐明。本研究在三种髓系白血病细胞系中发现，仅c-Myc可对苦参碱处理产生快速应答，且苦参碱可同时抑制c-Myc的转录与翻译过程。作为c-Myc下游关键通路的核糖体生物发生与核苷酸代谢，在苦参碱处理后均受到显著抑制。综上，本研究结果证实，苦参碱是一类特殊的c-Myc抑制剂，可通过在髓系白血病中抑制c-Myc的表达，进而阻断核糖体生物发生与核苷酸代谢通路。本研究为靶向c-Myc驱动型癌症的苦参碱衍生物开发提供了科学依据。