8-Hydroxydaidzein Induces Apoptosis and Inhibits AML-Associated Gene Expression in U-937 Cells: Potential Phytochemical for AML Treatment

doi:10.3390/biom13111575

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Title:	8-Hydroxydaidzein Induces Apoptosis and Inhibits AML-Associated Gene Expression in U-937 Cells: Potential Phytochemical for AML Treatment
Authors:	Wu, Pei-Shan Wang, Chih-Yang Hsu, Hao-Jen Yen, Jui-Hung Wu, Ming-Jiuan
Contributors:	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
Keywords:	8-hydroxydaidzein apoptosis CDK6 caspase-7 acute myeloid leukemia
Date:	2023
Issue Date:	2024-12-25 11:03:54 (UTC+8)
Publisher:	MDPI
Abstract:	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.
Relation:	Biomolecules, v.13, n.11, Article 1575
Appears in Collections:	[Dept. of Pharmacy] Periodical Articles [Dept. of Biotechnology (including master's program)] Periodical Articles

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