8-Hydroxydaidzein, an Isoflavone from Fermented Soybean, Induces Autophagy, Apoptosis, Differentiation, and Degradation of Oncoprotein BCR-ABL in K562 Cells
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. W...
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MDPI AG
2020-11-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/8/11/506 |
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| author | Pei-Shan Wu Jui-Hung Yen Chih-Yang Wang Pei-Yi Chen Jui-Hsiang Hung Ming-Jiuan Wu |
| author_facet | Pei-Shan Wu Jui-Hung Yen Chih-Yang Wang Pei-Yi Chen Jui-Hsiang Hung Ming-Jiuan Wu |
| author_sort | Pei-Shan Wu |
| collection | DOAJ |
| description | 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<sup>Cip1</sup> 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, <i>CD61</i> and <i>CD42b</i>, 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 μM) treatment for 48 h. Bioinformatics analysis of DEGs showed that hemopoiesis, cell cycle regulation, nuclear factor-κB (NF-κB), 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-κB 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. |
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| language | English |
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| spelling | doaj.art-0f8b8af76bae46499347ff38f01e97fc2023-11-20T21:08:25ZengMDPI AGBiomedicines2227-90592020-11-0181150610.3390/biomedicines81105068-Hydroxydaidzein, an Isoflavone from Fermented Soybean, Induces Autophagy, Apoptosis, Differentiation, and Degradation of Oncoprotein BCR-ABL in K562 CellsPei-Shan Wu0Jui-Hung Yen1Chih-Yang Wang2Pei-Yi Chen3Jui-Hsiang Hung4Ming-Jiuan Wu5Department of Pharmacy, Chia Nan University of Pharmacy and Science, Tainan 717, TaiwanDepartment of Molecular Biology and Human Genetics, Tzu Chi University, Hualien 970, TaiwanPh.D. Program for Cancer Molecular Biology and Drug Discovery, Taipei Medical University, Taipei 11031, TaiwanDepartment of Molecular Biology and Human Genetics, Tzu Chi University, Hualien 970, TaiwanDepartment of Biotechnology, Chia Nan University of Pharmacy and Science, Tainan 717, TaiwanDepartment of Pharmacy, Chia Nan University of Pharmacy and Science, Tainan 717, Taiwan8-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<sup>Cip1</sup> 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, <i>CD61</i> and <i>CD42b</i>, 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 μM) treatment for 48 h. Bioinformatics analysis of DEGs showed that hemopoiesis, cell cycle regulation, nuclear factor-κB (NF-κB), 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-κB 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.https://www.mdpi.com/2227-9059/8/11/506K5628-hydroxydaidzeinapoptosisautophagyBCR-ABLMAPK |
| spellingShingle | Pei-Shan Wu Jui-Hung Yen Chih-Yang Wang Pei-Yi Chen Jui-Hsiang Hung Ming-Jiuan Wu 8-Hydroxydaidzein, an Isoflavone from Fermented Soybean, Induces Autophagy, Apoptosis, Differentiation, and Degradation of Oncoprotein BCR-ABL in K562 Cells Biomedicines K562 8-hydroxydaidzein apoptosis autophagy BCR-ABL MAPK |
| title | 8-Hydroxydaidzein, an Isoflavone from Fermented Soybean, Induces Autophagy, Apoptosis, Differentiation, and Degradation of Oncoprotein BCR-ABL in K562 Cells |
| title_full | 8-Hydroxydaidzein, an Isoflavone from Fermented Soybean, Induces Autophagy, Apoptosis, Differentiation, and Degradation of Oncoprotein BCR-ABL in K562 Cells |
| title_fullStr | 8-Hydroxydaidzein, an Isoflavone from Fermented Soybean, Induces Autophagy, Apoptosis, Differentiation, and Degradation of Oncoprotein BCR-ABL in K562 Cells |
| title_full_unstemmed | 8-Hydroxydaidzein, an Isoflavone from Fermented Soybean, Induces Autophagy, Apoptosis, Differentiation, and Degradation of Oncoprotein BCR-ABL in K562 Cells |
| title_short | 8-Hydroxydaidzein, an Isoflavone from Fermented Soybean, Induces Autophagy, Apoptosis, Differentiation, and Degradation of Oncoprotein BCR-ABL in K562 Cells |
| title_sort | 8 hydroxydaidzein an isoflavone from fermented soybean induces autophagy apoptosis differentiation and degradation of oncoprotein bcr abl in k562 cells |
| topic | K562 8-hydroxydaidzein apoptosis autophagy BCR-ABL MAPK |
| url | https://www.mdpi.com/2227-9059/8/11/506 |
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