School of Life Sciences, Peking University , Beijing 100871, People's Republic of China.
Hongqiao International Institute of Medicine, Shanghai Tongren Hospital/Faculty of Basic Medicine, Chemical Biology Division of Shanghai Universities E-Institutes, Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine , Shanghai 200025, People's Republic of China.
J Nat Prod. 2018 Feb 23;81(2):298-306. doi: 10.1021/acs.jnatprod.7b00722. Epub 2018 Feb 2.
Acute myeloid leukemia (AML) is a hematologic malignancy that is characterized by clonal proliferation of myeloid blasts. Despite the progress that has been made in the treatment of various malignant hematopoietic diseases, the effective treatment of AML remains very challenging. Differentiation therapy has emerged as a promising approach for leukemia treatment, and new and effective chemical agents to trigger the differentiation of AML cells, especially drug-resistant cells, are urgently required. Herein, the natural product jungermannenone C, a tetracyclic diterpenoid isolated from liverworts, is reported to induce cell differentiation in AML cells. Interestingly, the unnatural enantiomer of jungermannenone C (1) was found to be more potent than jungermannenone C in inducing cell differentiation. Furthermore, compound 1 targets peroxiredoxins I and II by selectively binding to the conserved cysteine residues and leads to cellular reactive oxygen species accumulation. Accordingly, ent-jungermannenone C (1) shows potential for further investigation as an effective differentiation therapy against AML.
急性髓系白血病（AML）是一种血液系统恶性肿瘤，其特征是髓性原始细胞的克隆性增殖。尽管在治疗各种恶性血液病方面取得了进展，但 AML 的有效治疗仍然极具挑战性。分化治疗已成为白血病治疗的一种有前途的方法，迫切需要新的、有效的化学试剂来诱导 AML 细胞，特别是耐药细胞的分化。本文报道了一种从地钱属植物中分离得到的四环二萜 jungermannenone C 可诱导 AML 细胞分化。有趣的是，jungermannenone C 的非天然对映异构体（1）在诱导细胞分化方面比 jungermannenone C 更有效。此外，化合物 1 通过选择性结合保守的半胱氨酸残基靶向过氧化物还原酶 I 和 II，导致细胞内活性氧物质的积累。因此，ent-jungermannenone C（1）具有作为 AML 有效分化治疗药物的进一步研究潜力。
