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| 標題: | 8-Hydroxydaidzein Induces Apoptosis and Inhibits AML-Associated Gene Expression in U-937 Cells: Potential Phytochemical for AML Treatment |
| 作者: | Wu, Pei-Shan
Wang, Chih-Yang
Hsu, Hao-Jen
Yen, Jui-Hung
Wu, Ming-Jiuan |
| 貢獻者: | Chia Nan Univ Pharm & Sci, Dept Pharm
Chia Nan Univ Pharm & Sci, Dept Biotechnol
Taipei Med Univ, PhD Program Canc Mol Biol & Drug Discovery
Taipei Med Univ, Grad Inst Canc Biol & Drug Discovery
Tzu Chi Univ, Dept Biomed Sci & Engn
Tzu Chi Univ, Dept Mol Biol & Human Genet
Tzu Chi Univ, Inst Med Sci |
| 關鍵字: | 8-hydroxydaidzein
apoptosis
CDK6
caspase-7
acute myeloid leukemia |
| 日期: | 2023 |
| 上傳時間: | 2024-12-25 11:03:54 (UTC+8) |
| 出版者: | MDPI |
| 摘要: | Background: 8-hydroxydaidzein (8-OHD) is a compound derived from daidzein, known for its anti-inflammatory and anti-proliferative properties in K562 human chronic myeloid leukemia (CML) cells. However, its effects on acute myeloid leukemia (AML) cells have not been fully understood. Method: To investigate its potential anti-AML mechanism, we employed an integrated in vitro-in silico approach. Results: Our findings demonstrate that 8-OHD suppresses the expression of CDK6 and CCND2 proteins and induces cell apoptosis in U-937 cells by activating Caspase-7 and cleaving PARP-1. Microarray analysis revealed that 8-OHD downregulates differentially expressed genes (DEGs) associated with rRNA processing and ribosome biogenesis pathways. Moreover, AML-target genes, including CCND2, MYC, NPM1, FLT3, and TERT, were downregulated by 8-OHD. Additionally, molecular docking software predicted that 8-OHD has the potential to interact with CDK6, FLT3, and TERT proteins, thereby reducing their activity and inhibiting cell proliferation. Notably, we discovered a synergic pharmacological interaction between 8-OHD and cytarabine (Ara-C). Conclusions: Overall, this study provides insights into the therapeutic applications of 8-OHD in treating AML and elucidates its underlying mechanisms of action. |
| 關聯: | Biomolecules, v.13, n.11, Article 1575 |
| 顯示於類別: | [藥學系(所)] 期刊論文
[生物科技系(所)] 期刊論文
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