Antitumour effect of odoroside A and its derivative on human leukaemia cells through the ROS/JNK pathway
| Autor: | Chenyang Li, Qian Zhang, Xiaopeng Hu, Tie Chen, Shuquan Zhang, Xiaodong Wang |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
Time Factors MAP Kinase Signaling System HL60 Mice Nude Apoptosis HL-60 Cells Toxicology Flow cytometry Mice chemistry.chemical_compound Nude mouse In vivo Autophagy medicine Animals Humans Nerium Cell Proliferation Pharmacology Mice Inbred BALB C Leukemia Dose-Response Relationship Drug biology medicine.diagnostic_test Biological activity General Medicine biology.organism_classification Antineoplastic Agents Phytogenic Xenograft Model Antitumor Assays Molecular biology Cardenolides chemistry K562 Cells Reactive Oxygen Species K562 cells |
| Zdroj: | Basic & Clinical Pharmacology & Toxicology. 130:56-69 |
| ISSN: | 1742-7843 1742-7835 |
| Popis: | Oleandrigenin-3-O-β-D-diginoside (a derivative of odoroside A), isolated and purified by our group, has seldom been explored for its pharmacological activity. This study aimed at clarifying the mechanisms towards the leukaemia-suppressive role of odoroside A (compound #1) and its derivative, oleandrigenin-3-O-β-D-diginoside (compound #2) isolated from Nerium oleander. Viability and nuclear morphology change were assessed by CCK-8 assay and fluorescence microscope, respectively. Then, the cell apoptosis and autophagy induced by the compounds were detected by flow cytometry and Western blot. Xenograft model of nude mice was also applied to measure the leukaemia-suppressive effects of compound #2 in vivo. The result displayed that compound #1 and compound #2 inhibited the proliferation of HL60 and K562 cells and stronger effects were found in HL60 than K562 cells. Both of the compounds induced a dose-dependent apoptosis and autophagy in HL60 cells, where compound #2 was more potent than compound #1. Compound #2 also demonstrated a time-dependent apoptosis and autophagy in HL60 cells. Furthermore, ROS generation and JNK phosphorylation occurred in a dose-dependent manner in the cells treated with compound #2. Mitochondria also played critical role, proved by the decrease of Bcl-2, the release of cyto c to cytosol and the activation of caspase-3 and caspase-9. Moreover, the antitumour effects of compound #2 were validated in the nude mouse xenograft model in vivo. Odoroside A and its derivative inhibited the growth of leukaemia by inducing apoptosis and autophagy through the activation of ROS/JNK pathway. These results suggest that the compounds can serve as potential antitumour agents against leukaemia, especially acute myeloid leukaemia (AML). |
| Databáze: | OpenAIRE |
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