Genistein alleviates doxorubicin‐induced cardiomyocyte autophagy and apoptosis via ERK/STAT3/c‐Myc signaling pathway in rat model
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Wiley
2024
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| _version_ | 1867012655934341120 |
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| author | Jinxia Wu Ailu Feng Chunyang Liu Wenxiu Zhou Kexue Li Yan Liu Yue Shi Joseph Adu‐Amankwaah Hongli Yu Xiuhua Pan Hong Sun |
| author_facet | Jinxia Wu Ailu Feng Chunyang Liu Wenxiu Zhou Kexue Li Yan Liu Yue Shi Joseph Adu‐Amankwaah Hongli Yu Xiuhua Pan Hong Sun Jinxia Wu Ailu Feng Chunyang Liu Wenxiu Zhou Kexue Li Yan Liu Yue Shi Joseph Adu‐Amankwaah Hongli Yu Xiuhua Pan Hong Sun |
| collection | Wiley Open Access |
| contents | Genistein alleviates doxorubicin‐induced cardiomyocyte autophagy and apoptosis via ERK/STAT3/c‐Myc signaling pathway in rat model Jinxia Wu Ailu Feng Chunyang Liu Wenxiu Zhou Kexue Li Yan Liu Yue Shi Joseph Adu‐Amankwaah Hongli Yu Xiuhua Pan Hong Sun Phytotherapy Research AbstractDoxorubicin (Dox) is a highly effective anti‐neoplastic agent. Still, its utility in the clinic has been hindered by toxicities, including vomiting, hematopoietic suppression and nausea, with cardiotoxicity being the most serious side effect. Genistein (Gen) is a natural product with extensive biological effects, including anti‐oxidation, anti‐tumor, and cardiovascular protection. This study evaluated whether Gen protected the heart from Dox‐induced cardiotoxicity and explored the underlying mechanisms. Male Sprague–Dawley (SD) rats were categorized into control (Ctrl), genistein (Gen), doxorubicin (Dox), genistein 20 mg/kg/day + doxorubicin (Gen20 + Dox) and genistein 40 mg/kg/day + doxorubicin (Gen40 + Dox) groups. Six weeks after injection, immunohistochemistry (IHC), transmission electron microscopy (TEM), and clinical cardiac function analyses were performed to evaluate the effects of Dox on cardiac function and structural alterations. Furthermore, each heart histopathological lesions were given a score of 0–3 in compliance with the articles for statistical analysis. In addition, molecular and cellular response of H9c2 cells toward Dox were evaluated through western blotting, Cell Counting Kit‐8 (CCK8), AO staining and calcein AM/PI assay. Dox (5 μM in vitro and 18 mg/kg in vivo) was used in this study. In vivo, low‐dose Gen pretreatment protected the rat against Dox‐induced cardiac dysfunction and pathological remodeling. Gen inhibited extracellular signal‐regulated kinase1/2 (ERK1/2)'s phosphorylation, increased the protein levels of STAT3 and c‐Myc, and decreased the autophagy and apoptosis of cardiomyocytes. U0126, a MEK1/2 inhibitor, can mimic the effect of Gen in protecting against Dox‐induced cytotoxicity both in vivo and in vitro. Molecular docking analysis showed that Gen forms a stable complex with ERK1/2. Gen protected the heart against Dox‐induced cardiomyocyte autophagy and apoptosis through the ERK/STAT3/c‐Myc signaling pathway. 10.1002/ptr.8236 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| doi_str_mv | 10.1002/ptr.8236 |
| format | Artículo Open Access |
| id | wiley_oa_10_1002_ptr_8236 |
| institution | Wiley Open Access |
| license_str_mv | http://onlinelibrary.wiley.com/termsAndConditions#vor |
| publishDate | 2024 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | Genistein alleviates doxorubicin‐induced cardiomyocyte autophagy and apoptosis via ERK/STAT3/c‐Myc signaling pathway in rat model Jinxia Wu Ailu Feng Chunyang Liu Wenxiu Zhou Kexue Li Yan Liu Yue Shi Joseph Adu‐Amankwaah Hongli Yu Xiuhua Pan Hong Sun Phytotherapy Research Genistein alleviates doxorubicin‐induced cardiomyocyte autophagy and apoptosis via ERK/STAT3/c‐Myc signaling pathway in rat model Jinxia Wu Ailu Feng Chunyang Liu Wenxiu Zhou Kexue Li Yan Liu Yue Shi Joseph Adu‐Amankwaah Hongli Yu Xiuhua Pan Hong Sun Phytotherapy Research AbstractDoxorubicin (Dox) is a highly effective anti‐neoplastic agent. Still, its utility in the clinic has been hindered by toxicities, including vomiting, hematopoietic suppression and nausea, with cardiotoxicity being the most serious side effect. Genistein (Gen) is a natural product with extensive biological effects, including anti‐oxidation, anti‐tumor, and cardiovascular protection. This study evaluated whether Gen protected the heart from Dox‐induced cardiotoxicity and explored the underlying mechanisms. Male Sprague–Dawley (SD) rats were categorized into control (Ctrl), genistein (Gen), doxorubicin (Dox), genistein 20 mg/kg/day + doxorubicin (Gen20 + Dox) and genistein 40 mg/kg/day + doxorubicin (Gen40 + Dox) groups. Six weeks after injection, immunohistochemistry (IHC), transmission electron microscopy (TEM), and clinical cardiac function analyses were performed to evaluate the effects of Dox on cardiac function and structural alterations. Furthermore, each heart histopathological lesions were given a score of 0–3 in compliance with the articles for statistical analysis. In addition, molecular and cellular response of H9c2 cells toward Dox were evaluated through western blotting, Cell Counting Kit‐8 (CCK8), AO staining and calcein AM/PI assay. Dox (5 μM in vitro and 18 mg/kg in vivo) was used in this study. In vivo, low‐dose Gen pretreatment protected the rat against Dox‐induced cardiac dysfunction and pathological remodeling. Gen inhibited extracellular signal‐regulated kinase1/2 (ERK1/2)'s phosphorylation, increased the protein levels of STAT3 and c‐Myc, and decreased the autophagy and apoptosis of cardiomyocytes. U0126, a MEK1/2 inhibitor, can mimic the effect of Gen in protecting against Dox‐induced cytotoxicity both in vivo and in vitro. Molecular docking analysis showed that Gen forms a stable complex with ERK1/2. Gen protected the heart against Dox‐induced cardiomyocyte autophagy and apoptosis through the ERK/STAT3/c‐Myc signaling pathway. 10.1002/ptr.8236 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| title | Genistein alleviates doxorubicin‐induced cardiomyocyte autophagy and apoptosis via ERK/STAT3/c‐Myc signaling pathway in rat model |
| topic | Phytotherapy Research |
| url | https://onlinelibrary.wiley.com/doi/10.1002/ptr.8236 |