Ginsenoside Rh2 mitigates doxorubicin‐induced cardiotoxicity by inhibiting apoptotic and inflammatory damage and weakening pathological remodelling in breast cancer‐bearing mice
Objectives There are presently a few viable ways to reduce cardiotoxicity of doxorubicin (Dox). The combination of chemotherapy agents with natural compounds delivers greater efficacy and reduces adverse effects in recent researches for cancer treatment. Here, we examined the potential effect of gin...
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Published in | Cell proliferation Vol. 55; no. 6; pp. e13246 - n/a |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
England
John Wiley & Sons, Inc
01.06.2022
John Wiley and Sons Inc |
Subjects | |
Online Access | Get full text |
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Summary: | Objectives
There are presently a few viable ways to reduce cardiotoxicity of doxorubicin (Dox). The combination of chemotherapy agents with natural compounds delivers greater efficacy and reduces adverse effects in recent researches for cancer treatment. Here, we examined the potential effect of ginsenoside Rh2 on a Dox‐based regimen in chemotherapy treatment.
Materials and Methods
Human breast tumour (MDA‐MB‐231) xenograft nude mice, human cardiac ventricle fibroblasts, and human umbilical vein endothelial cells (HUVEC) were employed in the present study. Histology, immunohistochemistry, immunofluorescence, western blot, antibody array, and RNA‐sequencing analyses were utilized to assess the protective effect of Rh2 on cardiotoxicity induced by Dox and the underlying mechanisms.
Results
Rh2‐reduced cardiotoxicity by inhibiting the cardiac histopathological changes, apoptosis and necrosis, and consequent inflammation. Pathological remodelling was attenuated by reducing fibroblast to myofibroblast transition (FMT) and endothelial–mesenchymal transition (EndMT) in hearts. RNA‐sequencing analysis showed that Dox treatment predominantly targets cell cycle and attachment of microtubules and boosted tumour necrosis, chemokine and interferon‐gamma production, response to cytokine and chemokine, and T cell activation, whereas Rh2 regulated these effects. Intriguingly, Rh2 also attenuated fibrosis via promoting senescence in myofibroblasts and reversing established myofibroblast differentiation in EndMT.
Conclusions
Rh2 regulates multiple pathways in the Dox‐provoked heart, proposing a potential candidate for cancer supplement and therapy‐associated cardiotoxicity.
Doxorubicin is extensively reported to induce severe cardiotoxicity in clinical applications. Our work proposed a natural herbal compound, ginsenoside Rh2, as a potential candidate for attenuating this side effect. Rh2 significantly inhibited cardiac apoptosis and necrosis, inflammation, and pathological remodelling in Dox‐challenged hearts. |
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Bibliography: | Funding information Advancement of Active Biomedical material Project, funded by the Ministry of Trade, Grant/Award Number: P0014633; Development of industrialization technology for crop virus and pest Project, funded by the Ministry of Agriculture, Food and Rural Affairs, Grant/Award Number: 321109041SB010; Intelligent Synthetic Biology Center of the Global Frontier Project, funded by the Ministry of Education, Science and Technology, Grant/Award Number: 2011‐0031955; KAIST Cross‐Generation Collaborative Lab project; Multi‐Department Research and Business Development Program, funded by Sejong city, Grant/Award Number: 2021‐153‐0028‐0019‐002B; The Bio‐Synergy Research Project of the Ministry of Science, ICT and Future Planning through the National Research Foundation, Grant/Award Number: NRF‐2021M3A9C4001028 Jingang Hou and Yeejin Yun should be considered joint first author. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Funding information Advancement of Active Biomedical material Project, funded by the Ministry of Trade, Grant/Award Number: P0014633; Development of industrialization technology for crop virus and pest Project, funded by the Ministry of Agriculture, Food and Rural Affairs, Grant/Award Number: 321109041SB010; Intelligent Synthetic Biology Center of the Global Frontier Project, funded by the Ministry of Education, Science and Technology, Grant/Award Number: 2011‐0031955; KAIST Cross‐Generation Collaborative Lab project; Multi‐Department Research and Business Development Program, funded by Sejong city, Grant/Award Number: 2021‐153‐0028‐0019‐002B; The Bio‐Synergy Research Project of the Ministry of Science, ICT and Future Planning through the National Research Foundation, Grant/Award Number: NRF‐2021M3A9C4001028 |
ISSN: | 0960-7722 1365-2184 |
DOI: | 10.1111/cpr.13246 |