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ent-Jungermannenone C Triggers Reactive Oxygen Species-Dependent Cell Differentiation in Leukemia Cells
- Source :
- Journal of Natural Products. 81:298-306
- Publication Year :
- 2018
- Publisher :
- American Chemical Society (ACS), 2018.
-
Abstract
- 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.
- Subjects :
- Hepatophyta
0301 basic medicine
Myeloid
Cellular differentiation
Pharmaceutical Science
Analytical Chemistry
03 medical and health sciences
0302 clinical medicine
Differentiation therapy
Cell Line, Tumor
hemic and lymphatic diseases
Drug Discovery
medicine
Humans
Cell Proliferation
Pharmacology
chemistry.chemical_classification
Reactive oxygen species
Chemistry
Organic Chemistry
Myeloid leukemia
Cell Differentiation
Peroxiredoxins
medicine.disease
Leukemia, Myeloid, Acute
Leukemia
Haematopoiesis
030104 developmental biology
medicine.anatomical_structure
Complementary and alternative medicine
Drug Resistance, Neoplasm
Cell culture
030220 oncology & carcinogenesis
Cancer research
Molecular Medicine
Diterpenes
Reactive Oxygen Species
Subjects
Details
- ISSN :
- 15206025 and 01633864
- Volume :
- 81
- Database :
- OpenAIRE
- Journal :
- Journal of Natural Products
- Accession number :
- edsair.doi.dedup.....503fb8df0b568dc8e9cec30d03e0eea8