Thiostrepton induces apoptotic cell death at the level of BCL-2/CED-9 in C. elegans
Abstract Thiostrepton, a thiopeptide antibiotic, has been attracting increasing attention for its anti-proliferative and anti-cancer properties in various tested cell culture models. Extensive in vitro analysis has been conducted to understand its anti-cancer effect across multiple cancer types and...
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Nature Portfolio
2025-07-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-09446-5 |
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| author | Alanoud Al-Kaabi Tayyiba Akbar Ali Mahmoud Izadi Kirti S. Prabhu Shahab Uddin Ehsan Pourkarimi |
| author_facet | Alanoud Al-Kaabi Tayyiba Akbar Ali Mahmoud Izadi Kirti S. Prabhu Shahab Uddin Ehsan Pourkarimi |
| author_sort | Alanoud Al-Kaabi |
| collection | DOAJ |
| description | Abstract Thiostrepton, a thiopeptide antibiotic, has been attracting increasing attention for its anti-proliferative and anti-cancer properties in various tested cell culture models. Extensive in vitro analysis has been conducted to understand its anti-cancer effect across multiple cancer types and cell lines, with numerous reports indicating that thiostrepton can inhibit cancer cell proliferation and tumor growth and induce apoptosis in vitro. On the other hand, the in vivo anti-tumor effect of thiostrepton remains elusive. In this study, we aimed to genetically and physiologically characterize the effects of thiostrepton on apoptosis induction in vivo using C. elegans. Our data demonstrate that thiostrepton induces apoptosis in C. elegans, and this apoptotic induction is independent of the genomic instability and is not related to p53 activity. Rather, the apoptotic cell death mediated by thiostrepton treatment occurs at the level of the BCL-2/CED-9 protein at the core apoptotic machinery. Furthermore, we have unlinked the high ROS (reactive oxygen species) induction reported in earlier in vitro studies from apoptosis induction upon thiostrepton treatment in C. elegans. Overall, our genetic data indicate that apoptosis induction mediated by thiostrepton occurs at the level of the core apoptotic machinery. |
| format | Article |
| id | doaj-art-5a4da7c53ee043d3971ba0f4a786ed10 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-5a4da7c53ee043d3971ba0f4a786ed102025-08-20T04:01:51ZengNature PortfolioScientific Reports2045-23222025-07-0115111110.1038/s41598-025-09446-5Thiostrepton induces apoptotic cell death at the level of BCL-2/CED-9 in C. elegansAlanoud Al-Kaabi0Tayyiba Akbar Ali1Mahmoud Izadi2Kirti S. Prabhu3Shahab Uddin4Ehsan Pourkarimi5Division of Genomics and Translational Medicine, College of Health and Life Sciences, Hamad Bin Khalifa UniversityDivision of Genomics and Translational Medicine, College of Health and Life Sciences, Hamad Bin Khalifa UniversityDivision of Genomics and Translational Medicine, College of Health and Life Sciences, Hamad Bin Khalifa UniversityTranslational Research Institute, Academic Health System, Hamad Medical CorporationTranslational Research Institute, Academic Health System, Hamad Medical CorporationDivision of Genomics and Translational Medicine, College of Health and Life Sciences, Hamad Bin Khalifa UniversityAbstract Thiostrepton, a thiopeptide antibiotic, has been attracting increasing attention for its anti-proliferative and anti-cancer properties in various tested cell culture models. Extensive in vitro analysis has been conducted to understand its anti-cancer effect across multiple cancer types and cell lines, with numerous reports indicating that thiostrepton can inhibit cancer cell proliferation and tumor growth and induce apoptosis in vitro. On the other hand, the in vivo anti-tumor effect of thiostrepton remains elusive. In this study, we aimed to genetically and physiologically characterize the effects of thiostrepton on apoptosis induction in vivo using C. elegans. Our data demonstrate that thiostrepton induces apoptosis in C. elegans, and this apoptotic induction is independent of the genomic instability and is not related to p53 activity. Rather, the apoptotic cell death mediated by thiostrepton treatment occurs at the level of the BCL-2/CED-9 protein at the core apoptotic machinery. Furthermore, we have unlinked the high ROS (reactive oxygen species) induction reported in earlier in vitro studies from apoptosis induction upon thiostrepton treatment in C. elegans. Overall, our genetic data indicate that apoptosis induction mediated by thiostrepton occurs at the level of the core apoptotic machinery.https://doi.org/10.1038/s41598-025-09446-5CancerThiostreptonApoptosisBCL-2/CED-9C. elegansROS |
| spellingShingle | Alanoud Al-Kaabi Tayyiba Akbar Ali Mahmoud Izadi Kirti S. Prabhu Shahab Uddin Ehsan Pourkarimi Thiostrepton induces apoptotic cell death at the level of BCL-2/CED-9 in C. elegans Scientific Reports Cancer Thiostrepton Apoptosis BCL-2/CED-9 C. elegans ROS |
| title | Thiostrepton induces apoptotic cell death at the level of BCL-2/CED-9 in C. elegans |
| title_full | Thiostrepton induces apoptotic cell death at the level of BCL-2/CED-9 in C. elegans |
| title_fullStr | Thiostrepton induces apoptotic cell death at the level of BCL-2/CED-9 in C. elegans |
| title_full_unstemmed | Thiostrepton induces apoptotic cell death at the level of BCL-2/CED-9 in C. elegans |
| title_short | Thiostrepton induces apoptotic cell death at the level of BCL-2/CED-9 in C. elegans |
| title_sort | thiostrepton induces apoptotic cell death at the level of bcl 2 ced 9 in c elegans |
| topic | Cancer Thiostrepton Apoptosis BCL-2/CED-9 C. elegans ROS |
| url | https://doi.org/10.1038/s41598-025-09446-5 |
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