8-Hydroxydaidzein, an Isoflavone from Fermented Soybean, Induces Autophagy, Apoptosis, Differentiation, and Degradation of Oncoprotein BCR-ABL in K562 Cells

doi:10.3390/biomedicines8110506

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Title:	8-Hydroxydaidzein, an Isoflavone from Fermented Soybean, Induces Autophagy, Apoptosis, Differentiation, and Degradation of Oncoprotein BCR-ABL in K562 Cells
Authors:	Wu, Pei-Shan Yen, Jui-Hung Wang, Chih-Yang Chen, Pei-Yi Hung, Jui-Hsiang Wu, Ming-Jiuan
Contributors:	Chia Nan Univ Pharm & Sci, Dept Pharm Tzu Chi Univ, Dept Mol Biol & Human Genet Tzu Chi Univ, Inst Med Sci Taipei Med Univ, PhD Program Canc Mol Biol & Drug Discovery Taipei Med Univ, Grad Inst Canc Biol & Drug Discovery Tzu Chi Gen Hosp, Ctr Med Genet Chia Nan Univ Pharm & Sci, Dept Biotechnol
Keywords:	K562 8-hydroxydaidzein apoptosis autophagy BCR-ABL MAPK NF-kappa B
Date:	2020
Issue Date:	2022-11-18 11:21:43 (UTC+8)
Publisher:	Mdpi
Abstract:	8-Hydroxydaidzein (8-OHD, 7,8,4 '-trihydoxyisoflavone) is a hydroxylated derivative of daidzein isolated from fermented soybean products. The aim of this study is to investigate the anti-proliferative effects and the underlying mechanisms of 8-OHD in K562 human chronic myeloid leukemia (CML) cells. We found that 8-OHD induced reactive oxygen species (ROS) overproduction and cell cycle arrest at the S phase by upregulating p21(Cip1) and downregulating cyclin D2 (CCND2) and cyclin-dependent kinase 6 (CDK6) expression. 8-OHD also induced autophagy, caspase-7-dependent apoptosis, and the degradation of BCR-ABL oncoprotein. 8-OHD promoted Early Growth Response 1 (EGR1)-mediated megakaryocytic differentiation as an increased expression of marker genes, CD61 and CD42b, and the formation of multi-lobulated nuclei in enlarged K562 cells. A microarray-based transcriptome analysis revealed a total of 3174 differentially expressed genes (DEGs) after 8-OHD (100 mu M) treatment for 48 h. Bioinformatics analysis of DEGs showed that hemopoiesis, cell cycle regulation, nuclear factor-kappa B (NF-kappa B), and mitogen-activated protein kinase (MAPK) and Janus kinase/signal transducers and activators of transcription (JAK-STAT)-mediated apoptosis/anti-apoptosis networks were significantly regulated by 8-OHD. Western blot analysis confirmed that 8-OHD significantly induced the activation of MAPK and NF-kappa B signaling pathways, both of which may be responsible, at least in part, for the stimulation of apoptosis, autophagy, and differentiation in K562 cells. This is the first report on the anti-CML effects of 8-OHD and the combination of experimental and in silico analyses could provide a better understanding for the development of 8-OHD on CML therapy.
Relation:	Biomedicines, v.8, n.11, pp.23
Appears in Collections:	[Dept. of Pharmacy] Periodical Articles [Dept. of Biotechnology (including master's program)] Periodical Articles

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