Therapeutic potential of brentuximab vedotin in breast cancer and lymphoma via targeted apoptosis and gene regulation
Abstract This study was designed to assess the effect of brentuximab vedotin on several breast cancer cell lines in terms of promoting apoptosis and managing cancer progression. Additionally, the study investigated the potential of repurposing this drug for new therapeutic reasons, beyond its origin...
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Nature Portfolio
2025-01-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-84744-y |
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| author | Abeer Ezzat Mohga Shafiek Shimaa Shawki Shaimaa Abdel-Ghany Mahmoud Nazih Hussein Sabit |
| author_facet | Abeer Ezzat Mohga Shafiek Shimaa Shawki Shaimaa Abdel-Ghany Mahmoud Nazih Hussein Sabit |
| author_sort | Abeer Ezzat |
| collection | DOAJ |
| description | Abstract This study was designed to assess the effect of brentuximab vedotin on several breast cancer cell lines in terms of promoting apoptosis and managing cancer progression. Additionally, the study investigated the potential of repurposing this drug for new therapeutic reasons, beyond its original indications. The study evaluates the cytotoxic effects of Brentuximab vedotin across five cell lines: normal human skin fibroblasts (HSF), three breast cancer cell lines (MCF-7, MDA-MB-231, and T-47D), and histiocytic lymphoma (U-937). Brentuximab treatment was administered at four time points (0, 24, 48, and 72 h), with cell viability assessed at each interval. HSF cells, serving as controls, exhibited minimal viability loss (above 70%), indicating limited toxicity in normal fibroblasts. In contrast, MCF-7 and MDA-MB-231 cells demonstrated time-dependent reductions in viability, with a pronounced decline by 72 h, suggesting Brentuximab’s efficacy in both ER-positive and triple-negative breast cancer. T-47D cells also showed decreased viability, though at a slower rate. U-937 cells exhibited the most substantial reduction, highlighting Brentuximab’s potent activity against hematologic malignancies. Wound healing assays further revealed that Brentuximab significantly impaired the migration and healing capacity of cancer cells compared to untreated controls. Additionally, cell cycle analysis indicated G2/M phase arrest in cancer cells, particularly in MCF-7 and MDA-MB-231, while HSF cells remained largely unaffected. Apoptosis detection confirmed Brentuximab-induced cell death, with significant increases in late apoptosis in cancer lines, especially by 72 h. Gene expression analysis revealed upregulation of pro-apoptotic genes (BAX, Caspase 3, and Caspase 9) in cancer cells, alongside a decrease in anti-apoptotic BCL-2 expression. These findings suggest Brentuximab’s selective cytotoxicity against cancer cells and its potential as an effective therapeutic agent, particularly in breast cancer and histiocytic lymphoma. |
| format | Article |
| id | doaj-art-f34c548b397c4467abe8a5df4ef457da |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-f34c548b397c4467abe8a5df4ef457da2025-01-19T12:23:29ZengNature PortfolioScientific Reports2045-23222025-01-0115111910.1038/s41598-024-84744-yTherapeutic potential of brentuximab vedotin in breast cancer and lymphoma via targeted apoptosis and gene regulationAbeer Ezzat0Mohga Shafiek1Shimaa Shawki2Shaimaa Abdel-Ghany3Mahmoud Nazih4Hussein Sabit5Department of Medical Biotechnology, College of Biotechnology, Misr University for Science and TechnologyDepartment of Chemistry, Faculty of Science, Helwan UniversityDepartment of Chemistry, Faculty of Science, Helwan UniversityDepartment of Environmental Biotechnology, College of Biotechnology, Misr University for Science and TechnologyScientific Office, Egyptian Society of Pharmacogenomics and Personalized Medicine (ESPM)Department of Medical Biotechnology, College of Biotechnology, Misr University for Science and TechnologyAbstract This study was designed to assess the effect of brentuximab vedotin on several breast cancer cell lines in terms of promoting apoptosis and managing cancer progression. Additionally, the study investigated the potential of repurposing this drug for new therapeutic reasons, beyond its original indications. The study evaluates the cytotoxic effects of Brentuximab vedotin across five cell lines: normal human skin fibroblasts (HSF), three breast cancer cell lines (MCF-7, MDA-MB-231, and T-47D), and histiocytic lymphoma (U-937). Brentuximab treatment was administered at four time points (0, 24, 48, and 72 h), with cell viability assessed at each interval. HSF cells, serving as controls, exhibited minimal viability loss (above 70%), indicating limited toxicity in normal fibroblasts. In contrast, MCF-7 and MDA-MB-231 cells demonstrated time-dependent reductions in viability, with a pronounced decline by 72 h, suggesting Brentuximab’s efficacy in both ER-positive and triple-negative breast cancer. T-47D cells also showed decreased viability, though at a slower rate. U-937 cells exhibited the most substantial reduction, highlighting Brentuximab’s potent activity against hematologic malignancies. Wound healing assays further revealed that Brentuximab significantly impaired the migration and healing capacity of cancer cells compared to untreated controls. Additionally, cell cycle analysis indicated G2/M phase arrest in cancer cells, particularly in MCF-7 and MDA-MB-231, while HSF cells remained largely unaffected. Apoptosis detection confirmed Brentuximab-induced cell death, with significant increases in late apoptosis in cancer lines, especially by 72 h. Gene expression analysis revealed upregulation of pro-apoptotic genes (BAX, Caspase 3, and Caspase 9) in cancer cells, alongside a decrease in anti-apoptotic BCL-2 expression. These findings suggest Brentuximab’s selective cytotoxicity against cancer cells and its potential as an effective therapeutic agent, particularly in breast cancer and histiocytic lymphoma.https://doi.org/10.1038/s41598-024-84744-yBrentuximabBreast cancerApoptosisCell cycle analysisGene expression |
| spellingShingle | Abeer Ezzat Mohga Shafiek Shimaa Shawki Shaimaa Abdel-Ghany Mahmoud Nazih Hussein Sabit Therapeutic potential of brentuximab vedotin in breast cancer and lymphoma via targeted apoptosis and gene regulation Scientific Reports Brentuximab Breast cancer Apoptosis Cell cycle analysis Gene expression |
| title | Therapeutic potential of brentuximab vedotin in breast cancer and lymphoma via targeted apoptosis and gene regulation |
| title_full | Therapeutic potential of brentuximab vedotin in breast cancer and lymphoma via targeted apoptosis and gene regulation |
| title_fullStr | Therapeutic potential of brentuximab vedotin in breast cancer and lymphoma via targeted apoptosis and gene regulation |
| title_full_unstemmed | Therapeutic potential of brentuximab vedotin in breast cancer and lymphoma via targeted apoptosis and gene regulation |
| title_short | Therapeutic potential of brentuximab vedotin in breast cancer and lymphoma via targeted apoptosis and gene regulation |
| title_sort | therapeutic potential of brentuximab vedotin in breast cancer and lymphoma via targeted apoptosis and gene regulation |
| topic | Brentuximab Breast cancer Apoptosis Cell cycle analysis Gene expression |
| url | https://doi.org/10.1038/s41598-024-84744-y |
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