Zhong Wang-Jing, Ma Lingdi, Yang Fanfan, Cao Jialin, Tan Junyu, Li Bohong
Laboratory Center, Huizhou Third People's Hospital, Affiliated Hospital of Guangzhou Medical University, Huizhou, China.
Laboratory Medicine Department, Longhua Center for Chronic Disease Control, Shenzhen, China.
Front Pharmacol. 2022 Oct 21;13:1027441. doi: 10.3389/fphar.2022.1027441. eCollection 2022.
Previous studies have shown that matrine, a natural compound extracted from the herb , 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.
先前的研究表明，从该草药中提取的天然化合物苦参碱具有良好的抗白血病作用，但其关键靶点和作用机制仍不清楚。在此，我们发现，在三种髓系白血病细胞系中，只有c-Myc能对苦参碱处理迅速作出反应，且苦参碱抑制c-Myc的转录和翻译。苦参碱处理后，c-Myc的关键下游——核糖体生物合成和核苷酸代谢受到显著抑制。因此，我们的结果证实，苦参碱是一种特殊的c-Myc抑制剂，它通过抑制髓系白血病中的c-Myc来抑制核糖体生物合成和核苷酸代谢。本研究为苦参碱衍生物用于c-Myc驱动的癌症的开发提供了科学依据。
