Exploring the anticancer mechanism of cardiac glycosides using proteome integral solubility alteration approach
Abstract Background and Aims Cardiac glycosides (CGs), traditionally used for heart failure, have shown potential as anti‐cancer agents. This study aims to explore their multifaceted mechanisms in cancer cell biology using proteome integral solubility alteration (PISA), focusing on the interaction w...
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| Format: | Article |
| Language: | English |
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Wiley
2024-09-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.70252 |
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| author | Wenjie Qin Yinhua Deng Huan Ren Yanling Liu Ling Liu Wenhui Liu Yuxi Zhao Chen Li Zhiling Yang |
| author_facet | Wenjie Qin Yinhua Deng Huan Ren Yanling Liu Ling Liu Wenhui Liu Yuxi Zhao Chen Li Zhiling Yang |
| author_sort | Wenjie Qin |
| collection | DOAJ |
| description | Abstract Background and Aims Cardiac glycosides (CGs), traditionally used for heart failure, have shown potential as anti‐cancer agents. This study aims to explore their multifaceted mechanisms in cancer cell biology using proteome integral solubility alteration (PISA), focusing on the interaction with key proteins implicated in cellular metabolism and mitochondrial function. Methods We conducted lysate‐based and intact‐cell PISA assays on cancer cells treated with CGs (Digoxin, Digitoxin, Ouabain) to analyze protein solubility changes. This was followed by mass spectrometric analysis and bioinformatics to identify differentially soluble proteins (DSPs). Molecular docking simulations were performed to predict protein‐CG interactions. Public data including gene expression changes upon CG treatment were re‐analyzed for validation. Results The PISA assays revealed CGs’ broad‐spectrum interactions, particularly affecting proteins like PKM2, ANXA2, SLC16A1, GOT2 and GLUD1. Molecular docking confirmed stable interactions between CGs and these DSPs. Re‐analysis of public data supported the impact of CGs on cancer metabolism and cell signaling pathways. Conclusion Our findings suggest that CGs could be repurposed for cancer therapy by modulating cellular processes. The PISA data provide insights into the polypharmacological effects of CGs, warranting further exploration of their mechanisms and clinical potential. |
| format | Article |
| id | doaj-art-cc1b17f8297848e1a3b4a1e74fc42a3f |
| institution | DOAJ |
| issn | 2045-7634 |
| language | English |
| publishDate | 2024-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj-art-cc1b17f8297848e1a3b4a1e74fc42a3f2025-08-20T03:05:53ZengWileyCancer Medicine2045-76342024-09-011318n/an/a10.1002/cam4.70252Exploring the anticancer mechanism of cardiac glycosides using proteome integral solubility alteration approachWenjie Qin0Yinhua Deng1Huan Ren2Yanling Liu3Ling Liu4Wenhui Liu5Yuxi Zhao6Chen Li7Zhiling Yang8Department of Pharmacy Hunan Provincial Peoples Hospital, (The First Affiliated Hospital of Hunan Normal University) Changsha ChinaDepartment of Pharmacy Hunan Provincial Peoples Hospital, (The First Affiliated Hospital of Hunan Normal University) Changsha ChinaDepartment of Pharmacy Hunan Provincial Peoples Hospital, (The First Affiliated Hospital of Hunan Normal University) Changsha ChinaDepartment of Pharmacy Hunan Provincial Peoples Hospital, (The First Affiliated Hospital of Hunan Normal University) Changsha ChinaDepartment of Pharmacy Hunan Provincial Peoples Hospital, (The First Affiliated Hospital of Hunan Normal University) Changsha ChinaDepartment of Pharmacy The Second Xiangya Hospital, Central South University Changsha ChinaShenzhen Wininnovate Bio‐Tech Co., Ltd Shenzhen ChinaDepartment of Pharmacy Hunan Provincial Peoples Hospital, (The First Affiliated Hospital of Hunan Normal University) Changsha ChinaDepartment of Pharmacy Hunan Provincial Peoples Hospital, (The First Affiliated Hospital of Hunan Normal University) Changsha ChinaAbstract Background and Aims Cardiac glycosides (CGs), traditionally used for heart failure, have shown potential as anti‐cancer agents. This study aims to explore their multifaceted mechanisms in cancer cell biology using proteome integral solubility alteration (PISA), focusing on the interaction with key proteins implicated in cellular metabolism and mitochondrial function. Methods We conducted lysate‐based and intact‐cell PISA assays on cancer cells treated with CGs (Digoxin, Digitoxin, Ouabain) to analyze protein solubility changes. This was followed by mass spectrometric analysis and bioinformatics to identify differentially soluble proteins (DSPs). Molecular docking simulations were performed to predict protein‐CG interactions. Public data including gene expression changes upon CG treatment were re‐analyzed for validation. Results The PISA assays revealed CGs’ broad‐spectrum interactions, particularly affecting proteins like PKM2, ANXA2, SLC16A1, GOT2 and GLUD1. Molecular docking confirmed stable interactions between CGs and these DSPs. Re‐analysis of public data supported the impact of CGs on cancer metabolism and cell signaling pathways. Conclusion Our findings suggest that CGs could be repurposed for cancer therapy by modulating cellular processes. The PISA data provide insights into the polypharmacological effects of CGs, warranting further exploration of their mechanisms and clinical potential.https://doi.org/10.1002/cam4.70252cardiac glycosidedigitoxindigoxindrug repositioningdrug repurposingoff‐target |
| spellingShingle | Wenjie Qin Yinhua Deng Huan Ren Yanling Liu Ling Liu Wenhui Liu Yuxi Zhao Chen Li Zhiling Yang Exploring the anticancer mechanism of cardiac glycosides using proteome integral solubility alteration approach Cancer Medicine cardiac glycoside digitoxin digoxin drug repositioning drug repurposing off‐target |
| title | Exploring the anticancer mechanism of cardiac glycosides using proteome integral solubility alteration approach |
| title_full | Exploring the anticancer mechanism of cardiac glycosides using proteome integral solubility alteration approach |
| title_fullStr | Exploring the anticancer mechanism of cardiac glycosides using proteome integral solubility alteration approach |
| title_full_unstemmed | Exploring the anticancer mechanism of cardiac glycosides using proteome integral solubility alteration approach |
| title_short | Exploring the anticancer mechanism of cardiac glycosides using proteome integral solubility alteration approach |
| title_sort | exploring the anticancer mechanism of cardiac glycosides using proteome integral solubility alteration approach |
| topic | cardiac glycoside digitoxin digoxin drug repositioning drug repurposing off‐target |
| url | https://doi.org/10.1002/cam4.70252 |
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