Video 2_Doxorubicin induces cardiotoxicity by enhancing autophagy via mTOR signaling in hiPSC- and hESC-derived cardiomyocytes.mp4
Introduction<p>Doxorubicin (DOX) is a highly effective anti-cancer drug, but its clinical applications are limited by its cardiotoxicity. The mechanisms underlying DOX-induced cardiotoxicity (DIC) remain incompletely understood. Human induced pluripotent stem cells (hiPSCs) and human embryonic...
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2025
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| _version_ | 1849927636190494720 |
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| author | Minxia Ke (4889887) |
| author2 | Hao Wang (39217) Kailun Yang (4685239) Meng Ji (305678) Nianmin Qi (14431644) Yuehong Wu (4889893) |
| author2_role | author author author author author |
| author_facet | Minxia Ke (4889887) Hao Wang (39217) Kailun Yang (4685239) Meng Ji (305678) Nianmin Qi (14431644) Yuehong Wu (4889893) |
| author_role | author |
| dc.creator.none.fl_str_mv | Minxia Ke (4889887) Hao Wang (39217) Kailun Yang (4685239) Meng Ji (305678) Nianmin Qi (14431644) Yuehong Wu (4889893) |
| dc.date.none.fl_str_mv | 2025-11-25T06:16:31Z |
| dc.identifier.none.fl_str_mv | 10.3389/fcell.2025.1616235.s002 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/media/Video_2_Doxorubicin_induces_cardiotoxicity_by_enhancing_autophagy_via_mTOR_signaling_in_hiPSC-_and_hESC-derived_cardiomyocytes_mp4/30703877 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Cell Biology doxorubicin cardiomyocytes autophagy MTOR signaling human induced pluripotent stem cells human embryonic stem cells |
| dc.title.none.fl_str_mv | Video 2_Doxorubicin induces cardiotoxicity by enhancing autophagy via mTOR signaling in hiPSC- and hESC-derived cardiomyocytes.mp4 |
| dc.type.none.fl_str_mv | Dataset Media info:eu-repo/semantics/publishedVersion dataset |
| description | Introduction<p>Doxorubicin (DOX) is a highly effective anti-cancer drug, but its clinical applications are limited by its cardiotoxicity. The mechanisms underlying DOX-induced cardiotoxicity (DIC) remain incompletely understood. Human induced pluripotent stem cells (hiPSCs) and human embryonic stem cells (hESCs) offer an advanced platform for investigating DIC, as they accurately recapitulate human cardiac physiology and pathology. However, the roles and mechanisms of DIC in hiPSC-CMs and hESC-CMs, especially regarding autophagy dynamics and regulation, are still not well-defined.</p>Methods<p>Cell viability, apoptosis, reactive oxygen species production, and DNA damage were assessed. Autophagy was evaluated by transmission electron microscope, LC3-II/LC3-I ratio, and autophagy flux assays. The role of autophagy and mTOR signaling was investigated using 3-methyladenine (3-MA) and rapamycin (RAPA), respectively.</p>Results<p>DOX reduced cell viability and induced apoptosis in hiPSC-CMs and hESC-CMs. Additionally, DOX caused an increase in reactive oxygen species production and DNA damage. Furthermore, DOX significantly upregulated autophagy, confirmed by the accumulation of autophagosomes and autolysosomes, and an increase in the LC3-II/LC3-I ratio. Autophagy flux assays showed that DOX induced autophagy in a time-dependent manner. The autophagy mediated by DOX was partially attenuated by 3-MA. Moreover, this activation was due to mTOR signaling inhibition. The downregulation of mTOR signaling by RAPA increased cell death of hESC-CMs. Interestingly, minor variations in injury severity and cellular sensitivity were observed between these two models.</p>Conclusion<p>Our study uncovered the multifaceted effects of DOX on hiPSC-CMs and hESC-CMs, revealing a shared mechanism in which DOX enhances autophagy via inhibition of the mTOR signaling pathway. These findings reveal key insights into DIC pathogenesis and suggest that autophagy modulation may be a promising therapeutic strategy.</p> |
| eu_rights_str_mv | openAccess |
| id | Manara_d6bfb39d63b70f2c97bfe4b719e1ee98 |
| identifier_str_mv | 10.3389/fcell.2025.1616235.s002 |
| network_acronym_str | Manara |
| network_name_str | ManaraRepo |
| oai_identifier_str | oai:figshare.com:article/30703877 |
| publishDate | 2025 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Video 2_Doxorubicin induces cardiotoxicity by enhancing autophagy via mTOR signaling in hiPSC- and hESC-derived cardiomyocytes.mp4Minxia Ke (4889887)Hao Wang (39217)Kailun Yang (4685239)Meng Ji (305678)Nianmin Qi (14431644)Yuehong Wu (4889893)Cell BiologydoxorubicincardiomyocytesautophagyMTOR signalinghuman induced pluripotent stem cellshuman embryonic stem cellsIntroduction<p>Doxorubicin (DOX) is a highly effective anti-cancer drug, but its clinical applications are limited by its cardiotoxicity. The mechanisms underlying DOX-induced cardiotoxicity (DIC) remain incompletely understood. Human induced pluripotent stem cells (hiPSCs) and human embryonic stem cells (hESCs) offer an advanced platform for investigating DIC, as they accurately recapitulate human cardiac physiology and pathology. However, the roles and mechanisms of DIC in hiPSC-CMs and hESC-CMs, especially regarding autophagy dynamics and regulation, are still not well-defined.</p>Methods<p>Cell viability, apoptosis, reactive oxygen species production, and DNA damage were assessed. Autophagy was evaluated by transmission electron microscope, LC3-II/LC3-I ratio, and autophagy flux assays. The role of autophagy and mTOR signaling was investigated using 3-methyladenine (3-MA) and rapamycin (RAPA), respectively.</p>Results<p>DOX reduced cell viability and induced apoptosis in hiPSC-CMs and hESC-CMs. Additionally, DOX caused an increase in reactive oxygen species production and DNA damage. Furthermore, DOX significantly upregulated autophagy, confirmed by the accumulation of autophagosomes and autolysosomes, and an increase in the LC3-II/LC3-I ratio. Autophagy flux assays showed that DOX induced autophagy in a time-dependent manner. The autophagy mediated by DOX was partially attenuated by 3-MA. Moreover, this activation was due to mTOR signaling inhibition. The downregulation of mTOR signaling by RAPA increased cell death of hESC-CMs. Interestingly, minor variations in injury severity and cellular sensitivity were observed between these two models.</p>Conclusion<p>Our study uncovered the multifaceted effects of DOX on hiPSC-CMs and hESC-CMs, revealing a shared mechanism in which DOX enhances autophagy via inhibition of the mTOR signaling pathway. These findings reveal key insights into DIC pathogenesis and suggest that autophagy modulation may be a promising therapeutic strategy.</p>2025-11-25T06:16:31ZDatasetMediainfo:eu-repo/semantics/publishedVersiondataset10.3389/fcell.2025.1616235.s002https://figshare.com/articles/media/Video_2_Doxorubicin_induces_cardiotoxicity_by_enhancing_autophagy_via_mTOR_signaling_in_hiPSC-_and_hESC-derived_cardiomyocytes_mp4/30703877CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/307038772025-11-25T06:16:31Z |
| spellingShingle | Video 2_Doxorubicin induces cardiotoxicity by enhancing autophagy via mTOR signaling in hiPSC- and hESC-derived cardiomyocytes.mp4 Minxia Ke (4889887) Cell Biology doxorubicin cardiomyocytes autophagy MTOR signaling human induced pluripotent stem cells human embryonic stem cells |
| status_str | publishedVersion |
| title | Video 2_Doxorubicin induces cardiotoxicity by enhancing autophagy via mTOR signaling in hiPSC- and hESC-derived cardiomyocytes.mp4 |
| title_full | Video 2_Doxorubicin induces cardiotoxicity by enhancing autophagy via mTOR signaling in hiPSC- and hESC-derived cardiomyocytes.mp4 |
| title_fullStr | Video 2_Doxorubicin induces cardiotoxicity by enhancing autophagy via mTOR signaling in hiPSC- and hESC-derived cardiomyocytes.mp4 |
| title_full_unstemmed | Video 2_Doxorubicin induces cardiotoxicity by enhancing autophagy via mTOR signaling in hiPSC- and hESC-derived cardiomyocytes.mp4 |
| title_short | Video 2_Doxorubicin induces cardiotoxicity by enhancing autophagy via mTOR signaling in hiPSC- and hESC-derived cardiomyocytes.mp4 |
| title_sort | Video 2_Doxorubicin induces cardiotoxicity by enhancing autophagy via mTOR signaling in hiPSC- and hESC-derived cardiomyocytes.mp4 |
| topic | Cell Biology doxorubicin cardiomyocytes autophagy MTOR signaling human induced pluripotent stem cells human embryonic stem cells |