Activation of PI3K/Akt mediates the protective effect of diallyl trisulfide on doxorubicin induced cardiac apoptosis
Diallyl trisulfide (DATS), an organosulfide compound derived from garlic, is renowned for its potent antioxidant properties, particularly in countering the generation of reactive oxygen species (ROS). It has also gained recognition as a potential agent for preventing heart-related conditions. Doxoru...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | Current Research in Toxicology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666027X23000348 |
| _version_ | 1797397540310614016 |
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| author | Su-Ying Wen Shang-Chuan Ng Wen-Kun Ho Han-Zhe Huang Chih-Yang Huang Wei-Wen Kuo |
| author_facet | Su-Ying Wen Shang-Chuan Ng Wen-Kun Ho Han-Zhe Huang Chih-Yang Huang Wei-Wen Kuo |
| author_sort | Su-Ying Wen |
| collection | DOAJ |
| description | Diallyl trisulfide (DATS), an organosulfide compound derived from garlic, is renowned for its potent antioxidant properties, particularly in countering the generation of reactive oxygen species (ROS). It has also gained recognition as a potential agent for preventing heart-related conditions. Doxorubicin (Dox), a commonly used chemotherapeutic drug, is known to induce severe cardiac complications by promoting ROS production. Therefore, it was imperative to investigate whether DATS possesses cardioprotective capabilities against Dox-induced cardiac apoptosis and elucidate the underlying mechanisms. In this study, we observed that the intracellular ROS levels and cardiac apoptosis were heightened in H9c2 cells exposed to Dox (1 μM). However, treatment with 10 μM DATS effectively mitigated the Dox-induced ROS generation and apoptotic signaling, concurrently activating the PI3K/Akt pathway. Notably, the anti-apoptotic effects of DATS were attenuated when PI3K siRNA and the LY294002 PI3K inhibitor were employed. Furthermore, the TUNEL assay results demonstrated a significant reduction in Dox-induced apoptosis with DATS treatment. In summary, our findings indicate that DATS can activate the PI3K/Akt pathway, reducing ROS production in cardiac cells exposed to Dox, and subsequently rescue cardiac cells from apoptosis. |
| first_indexed | 2024-03-09T01:11:31Z |
| format | Article |
| id | doaj.art-42b4f8d1216345f780a062a4da6b0334 |
| institution | Directory Open Access Journal |
| issn | 2666-027X |
| language | English |
| last_indexed | 2024-03-09T01:11:31Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Current Research in Toxicology |
| spelling | doaj.art-42b4f8d1216345f780a062a4da6b03342023-12-11T04:17:18ZengElsevierCurrent Research in Toxicology2666-027X2023-01-015100136Activation of PI3K/Akt mediates the protective effect of diallyl trisulfide on doxorubicin induced cardiac apoptosisSu-Ying Wen0Shang-Chuan Ng1Wen-Kun Ho2Han-Zhe Huang3Chih-Yang Huang4Wei-Wen Kuo5Department of Dermatology, Taipei City Hospital, Renai Branch, Taipei, Taiwan; Department of Cosmetic Applications and Management, Mackay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan; Department of Health Care Management, National Taipei University of Nursing and Health Sciences, Taipei, TaiwanDepartment of Biological Science and Technology, College of Life Sciences, China Medical University, Taichung, Taiwan; Ph.D. Program for Biotechnology Industry, China Medical University, Taichung, TaiwanDepartment of Biological Science and Technology, College of Life Sciences, China Medical University, Taichung, Taiwan; Ph.D. Program for Biotechnology Industry, China Medical University, Taichung, TaiwanDepartment of Biological Science and Technology, College of Life Sciences, China Medical University, Taichung, Taiwan; Ph.D. Program for Biotechnology Industry, China Medical University, Taichung, TaiwanGraduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan; Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan; Center of General Education, Buddhist Tzu Chi Medical Foundation, Tzu Chi University of Science and Technology, Hualien, Taiwan; Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan; Department of Biotechnology, Asia University, Taichung, TaiwanDepartment of Biological Science and Technology, College of Life Sciences, China Medical University, Taichung, Taiwan; Ph.D. Program for Biotechnology Industry, China Medical University, Taichung, Taiwan; Corresponding author at: Department of Biological Science and Technology, College of Life Sciences, China Medical University, Taichung, Taiwan.Diallyl trisulfide (DATS), an organosulfide compound derived from garlic, is renowned for its potent antioxidant properties, particularly in countering the generation of reactive oxygen species (ROS). It has also gained recognition as a potential agent for preventing heart-related conditions. Doxorubicin (Dox), a commonly used chemotherapeutic drug, is known to induce severe cardiac complications by promoting ROS production. Therefore, it was imperative to investigate whether DATS possesses cardioprotective capabilities against Dox-induced cardiac apoptosis and elucidate the underlying mechanisms. In this study, we observed that the intracellular ROS levels and cardiac apoptosis were heightened in H9c2 cells exposed to Dox (1 μM). However, treatment with 10 μM DATS effectively mitigated the Dox-induced ROS generation and apoptotic signaling, concurrently activating the PI3K/Akt pathway. Notably, the anti-apoptotic effects of DATS were attenuated when PI3K siRNA and the LY294002 PI3K inhibitor were employed. Furthermore, the TUNEL assay results demonstrated a significant reduction in Dox-induced apoptosis with DATS treatment. In summary, our findings indicate that DATS can activate the PI3K/Akt pathway, reducing ROS production in cardiac cells exposed to Dox, and subsequently rescue cardiac cells from apoptosis.http://www.sciencedirect.com/science/article/pii/S2666027X23000348Dially trisulfideDoxorubicinCardiac apoptosisReactive oxygen species |
| spellingShingle | Su-Ying Wen Shang-Chuan Ng Wen-Kun Ho Han-Zhe Huang Chih-Yang Huang Wei-Wen Kuo Activation of PI3K/Akt mediates the protective effect of diallyl trisulfide on doxorubicin induced cardiac apoptosis Current Research in Toxicology Dially trisulfide Doxorubicin Cardiac apoptosis Reactive oxygen species |
| title | Activation of PI3K/Akt mediates the protective effect of diallyl trisulfide on doxorubicin induced cardiac apoptosis |
| title_full | Activation of PI3K/Akt mediates the protective effect of diallyl trisulfide on doxorubicin induced cardiac apoptosis |
| title_fullStr | Activation of PI3K/Akt mediates the protective effect of diallyl trisulfide on doxorubicin induced cardiac apoptosis |
| title_full_unstemmed | Activation of PI3K/Akt mediates the protective effect of diallyl trisulfide on doxorubicin induced cardiac apoptosis |
| title_short | Activation of PI3K/Akt mediates the protective effect of diallyl trisulfide on doxorubicin induced cardiac apoptosis |
| title_sort | activation of pi3k akt mediates the protective effect of diallyl trisulfide on doxorubicin induced cardiac apoptosis |
| topic | Dially trisulfide Doxorubicin Cardiac apoptosis Reactive oxygen species |
| url | http://www.sciencedirect.com/science/article/pii/S2666027X23000348 |
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