Cell-Permeable Microprotein from Panax Ginseng Protects Against Doxorubicin-Induced Oxidative Stress and Cardiotoxicity
(1) Background: Doxorubicin (DOX) is a frontline chemotherapeutic, but its side-effects from oxidative stress, leading to cardiotoxicity, pose significant challenges to its clinical use. We recently discovered a novel family of proteolysis-resistant, cystine-dense, and cell-penetrating microproteins...
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MDPI AG
2025-04-01
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| Series: | Antioxidants |
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| author | Bamaprasad Dutta Shining Loo Antony Kam Xiaoliang Wang Na Wei Kathy Qian Luo Chuan-Fa Liu James P. Tam |
| author_facet | Bamaprasad Dutta Shining Loo Antony Kam Xiaoliang Wang Na Wei Kathy Qian Luo Chuan-Fa Liu James P. Tam |
| author_sort | Bamaprasad Dutta |
| collection | DOAJ |
| description | (1) Background: Doxorubicin (DOX) is a frontline chemotherapeutic, but its side-effects from oxidative stress, leading to cardiotoxicity, pose significant challenges to its clinical use. We recently discovered a novel family of proteolysis-resistant, cystine-dense, and cell-penetrating microproteins from <i>Panax ginseng</i> that we term ginsentides. Ginsentides, such as the 31-residue TP1, coordinate multiple biological systems to prevent vascular dysfunction and endoplasmic reticulum stress induced by internal and external stressors. (2) Methods: We assessed the protective effects of ginsentide TP1 on DOX-induced cardiotoxicity using both in vitro functional studies on H9c2 cardiomyocytes and in vivo animal models by zebrafish and ICR mouse models. In these models, we examined oxidative stress, apoptosis, intracellular calcium levels, mitochondrial function, inflammatory responses, and cardiac function. (3) Results: We show that ginsentide TP1 protects against DOX-induced cytotoxicity in the mitochondria-rich H9c2 cardiomyocytes and reduces myocardial injury in zebrafish and mice by mitigating oxidative stress, inflammation, calcium, and mitochondrial dysfunction, as well as apoptosis-mediated cell death. Importantly, TP1 preserves cellular homeostasis without compromising the anticancer potency of DOX in breast cancer cells. (4) Conclusions: our findings highlight a specific antioxidative function of ginsentide TP1 in managing DOX-induced cardiotoxicity during cancer treatment and provide a promising lead for developing cardioprotective peptides and microproteins against oxidative stress. |
| format | Article |
| id | doaj-art-9ba13b38069a4be5837b3f5f3ba4a8d3 |
| institution | OA Journals |
| issn | 2076-3921 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj-art-9ba13b38069a4be5837b3f5f3ba4a8d32025-08-20T02:28:16ZengMDPI AGAntioxidants2076-39212025-04-0114449310.3390/antiox14040493Cell-Permeable Microprotein from Panax Ginseng Protects Against Doxorubicin-Induced Oxidative Stress and CardiotoxicityBamaprasad Dutta0Shining Loo1Antony Kam2Xiaoliang Wang3Na Wei4Kathy Qian Luo5Chuan-Fa Liu6James P. Tam7School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, SingaporeSchool of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, SingaporeSchool of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, SingaporeSchool of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, SingaporeSchool of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 70 Nanyang Drive, Singapore 637457, SingaporeFaculty of Health Sciences, University of Macau, Taipa, Macao SAR, ChinaSchool of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, SingaporeSchool of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore(1) Background: Doxorubicin (DOX) is a frontline chemotherapeutic, but its side-effects from oxidative stress, leading to cardiotoxicity, pose significant challenges to its clinical use. We recently discovered a novel family of proteolysis-resistant, cystine-dense, and cell-penetrating microproteins from <i>Panax ginseng</i> that we term ginsentides. Ginsentides, such as the 31-residue TP1, coordinate multiple biological systems to prevent vascular dysfunction and endoplasmic reticulum stress induced by internal and external stressors. (2) Methods: We assessed the protective effects of ginsentide TP1 on DOX-induced cardiotoxicity using both in vitro functional studies on H9c2 cardiomyocytes and in vivo animal models by zebrafish and ICR mouse models. In these models, we examined oxidative stress, apoptosis, intracellular calcium levels, mitochondrial function, inflammatory responses, and cardiac function. (3) Results: We show that ginsentide TP1 protects against DOX-induced cytotoxicity in the mitochondria-rich H9c2 cardiomyocytes and reduces myocardial injury in zebrafish and mice by mitigating oxidative stress, inflammation, calcium, and mitochondrial dysfunction, as well as apoptosis-mediated cell death. Importantly, TP1 preserves cellular homeostasis without compromising the anticancer potency of DOX in breast cancer cells. (4) Conclusions: our findings highlight a specific antioxidative function of ginsentide TP1 in managing DOX-induced cardiotoxicity during cancer treatment and provide a promising lead for developing cardioprotective peptides and microproteins against oxidative stress.https://www.mdpi.com/2076-3921/14/4/493ginsentidecardioprotective adjuvantdoxorubicin-induced cardiotoxicityoxidative stressantioxidationcysteine-rich peptide |
| spellingShingle | Bamaprasad Dutta Shining Loo Antony Kam Xiaoliang Wang Na Wei Kathy Qian Luo Chuan-Fa Liu James P. Tam Cell-Permeable Microprotein from Panax Ginseng Protects Against Doxorubicin-Induced Oxidative Stress and Cardiotoxicity Antioxidants ginsentide cardioprotective adjuvant doxorubicin-induced cardiotoxicity oxidative stress antioxidation cysteine-rich peptide |
| title | Cell-Permeable Microprotein from Panax Ginseng Protects Against Doxorubicin-Induced Oxidative Stress and Cardiotoxicity |
| title_full | Cell-Permeable Microprotein from Panax Ginseng Protects Against Doxorubicin-Induced Oxidative Stress and Cardiotoxicity |
| title_fullStr | Cell-Permeable Microprotein from Panax Ginseng Protects Against Doxorubicin-Induced Oxidative Stress and Cardiotoxicity |
| title_full_unstemmed | Cell-Permeable Microprotein from Panax Ginseng Protects Against Doxorubicin-Induced Oxidative Stress and Cardiotoxicity |
| title_short | Cell-Permeable Microprotein from Panax Ginseng Protects Against Doxorubicin-Induced Oxidative Stress and Cardiotoxicity |
| title_sort | cell permeable microprotein from panax ginseng protects against doxorubicin induced oxidative stress and cardiotoxicity |
| topic | ginsentide cardioprotective adjuvant doxorubicin-induced cardiotoxicity oxidative stress antioxidation cysteine-rich peptide |
| url | https://www.mdpi.com/2076-3921/14/4/493 |
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