Trastuzumab Induces Apoptosis and Cell Cycle Arrest in Triple-Negative Breast Cancer, Suggesting Repurposing Potential
Background: Breast cancer remains the most common invasive cancer in women worldwide. Triple-negative breast cancer (TNBC) is an aggressive subtype with limited treatment options. Trastuzumab (Tz) is typically used to treat HER2-positive breast cancers, but its potential in TNBC is unclear. Objectiv...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2024-11-01
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| Series: | Breast Cancer: Basic and Clinical Research |
| Online Access: | https://doi.org/10.1177/11782234241285411 |
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| author | Shaimaa Abdel-Ghany Yasmin Khalid Soha Mohamed Gehan Mohamed Engy Mohdy Abeer Ezzat Engy F Madian Osama A Said Mohamed A Abdel-Hakeem Mahmoud Nazih Ahmed Khoder Hussein Sabit |
| author_facet | Shaimaa Abdel-Ghany Yasmin Khalid Soha Mohamed Gehan Mohamed Engy Mohdy Abeer Ezzat Engy F Madian Osama A Said Mohamed A Abdel-Hakeem Mahmoud Nazih Ahmed Khoder Hussein Sabit |
| author_sort | Shaimaa Abdel-Ghany |
| collection | DOAJ |
| description | Background: Breast cancer remains the most common invasive cancer in women worldwide. Triple-negative breast cancer (TNBC) is an aggressive subtype with limited treatment options. Trastuzumab (Tz) is typically used to treat HER2-positive breast cancers, but its potential in TNBC is unclear. Objectives: To investigate the effects of trastuzumab on cell viability, apoptosis, cell cycle progression, and gene expression in TNBC cell lines compared with HER2-positive and normal cell lines. Design: This is an in vitro experimental pre-clinical study using cultured cancer cell lines. Methods: MDA-MB-231 and 4T1 (TNBC), MCF-7 ( HER2 -positive), and HSF (normal) cell lines were treated with 20 μg/mL trastuzumab for 24 hours. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, apoptosis by flow cytometry, cell cycle progression by DNA content analysis, and gene expression by qPCR. Results: Trastuzumab significantly reduced cell viability and induced apoptosis in TNBC cell lines, comparable to effects in HER2-positive MCF-7 cells. Cell cycle analysis revealed G2/M phase arrest in TNBC cells. Gene expression analysis showed upregulation of ERBB2, NOTCH1 , EGFR , PIK3CA , and PTEN in MDA-MB-231 cells, while 4T1 cells exhibited downregulation of most genes except NOTCH1 . Conclusion: This study provides initial evidence for trastuzumab’s potential therapeutic effects in TNBC, despite low HER2 expression. The observed cytotoxicity, apoptosis induction, and cell cycle modulation in TNBC cells warrant further investigation into trastuzumab’s mechanisms of action in HER2 -negative contexts and its potential repurposing for TNBC treatment. |
| format | Article |
| id | doaj-art-3c1c95f91a754eb481b43ec387e5771d |
| institution | OA Journals |
| issn | 1178-2234 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Breast Cancer: Basic and Clinical Research |
| spelling | doaj-art-3c1c95f91a754eb481b43ec387e5771d2025-08-20T01:54:16ZengSAGE PublishingBreast Cancer: Basic and Clinical Research1178-22342024-11-011810.1177/11782234241285411Trastuzumab Induces Apoptosis and Cell Cycle Arrest in Triple-Negative Breast Cancer, Suggesting Repurposing PotentialShaimaa Abdel-Ghany0Yasmin Khalid1Soha Mohamed2Gehan Mohamed3Engy Mohdy4Abeer Ezzat5Engy F Madian6Osama A Said7Mohamed A Abdel-Hakeem8Mahmoud Nazih9Ahmed Khoder10Hussein Sabit11Department of Environmental Biotechnology, College of Biotechnology, Misr University for Science & Technology, Giza, EgyptDepartment of Environmental Biotechnology, College of Biotechnology, Misr University for Science & Technology, Giza, EgyptDepartment of Environmental Biotechnology, College of Biotechnology, Misr University for Science & Technology, Giza, EgyptDepartment of Environmental Biotechnology, College of Biotechnology, Misr University for Science & Technology, Giza, EgyptDepartment of Pharmaceutical Biotechnology, College of Biotechnology, Misr University for Science & Technology, Giza, EgyptDepartment of Medical Biotechnology, College of Biotechnology, Misr University for Science & Technology, Giza, EgyptDepartment of Medical Biotechnology, College of Biotechnology, Misr University for Science & Technology, Giza, EgyptDepartment of Agricultural Biotechnology, College of Biotechnology, Misr University for Science & Technology, Giza, EgyptDepartment of Pharmaceutical Biotechnology, College of Biotechnology, Misr University for Science & Technology, Giza, EgyptAl Ryada University for Science and Technology (RST), El-Mehwar ElMarkazy-2, Cairo - Alex desert RD K92, Giza, EgyptDepartment of Pharmacology, College of Pharmacy, Menofia University, EgyptDepartment of Medical Biotechnology, College of Biotechnology, Misr University for Science & Technology, Giza, EgyptBackground: Breast cancer remains the most common invasive cancer in women worldwide. Triple-negative breast cancer (TNBC) is an aggressive subtype with limited treatment options. Trastuzumab (Tz) is typically used to treat HER2-positive breast cancers, but its potential in TNBC is unclear. Objectives: To investigate the effects of trastuzumab on cell viability, apoptosis, cell cycle progression, and gene expression in TNBC cell lines compared with HER2-positive and normal cell lines. Design: This is an in vitro experimental pre-clinical study using cultured cancer cell lines. Methods: MDA-MB-231 and 4T1 (TNBC), MCF-7 ( HER2 -positive), and HSF (normal) cell lines were treated with 20 μg/mL trastuzumab for 24 hours. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, apoptosis by flow cytometry, cell cycle progression by DNA content analysis, and gene expression by qPCR. Results: Trastuzumab significantly reduced cell viability and induced apoptosis in TNBC cell lines, comparable to effects in HER2-positive MCF-7 cells. Cell cycle analysis revealed G2/M phase arrest in TNBC cells. Gene expression analysis showed upregulation of ERBB2, NOTCH1 , EGFR , PIK3CA , and PTEN in MDA-MB-231 cells, while 4T1 cells exhibited downregulation of most genes except NOTCH1 . Conclusion: This study provides initial evidence for trastuzumab’s potential therapeutic effects in TNBC, despite low HER2 expression. The observed cytotoxicity, apoptosis induction, and cell cycle modulation in TNBC cells warrant further investigation into trastuzumab’s mechanisms of action in HER2 -negative contexts and its potential repurposing for TNBC treatment.https://doi.org/10.1177/11782234241285411 |
| spellingShingle | Shaimaa Abdel-Ghany Yasmin Khalid Soha Mohamed Gehan Mohamed Engy Mohdy Abeer Ezzat Engy F Madian Osama A Said Mohamed A Abdel-Hakeem Mahmoud Nazih Ahmed Khoder Hussein Sabit Trastuzumab Induces Apoptosis and Cell Cycle Arrest in Triple-Negative Breast Cancer, Suggesting Repurposing Potential Breast Cancer: Basic and Clinical Research |
| title | Trastuzumab Induces Apoptosis and Cell Cycle Arrest in Triple-Negative Breast Cancer, Suggesting Repurposing Potential |
| title_full | Trastuzumab Induces Apoptosis and Cell Cycle Arrest in Triple-Negative Breast Cancer, Suggesting Repurposing Potential |
| title_fullStr | Trastuzumab Induces Apoptosis and Cell Cycle Arrest in Triple-Negative Breast Cancer, Suggesting Repurposing Potential |
| title_full_unstemmed | Trastuzumab Induces Apoptosis and Cell Cycle Arrest in Triple-Negative Breast Cancer, Suggesting Repurposing Potential |
| title_short | Trastuzumab Induces Apoptosis and Cell Cycle Arrest in Triple-Negative Breast Cancer, Suggesting Repurposing Potential |
| title_sort | trastuzumab induces apoptosis and cell cycle arrest in triple negative breast cancer suggesting repurposing potential |
| url | https://doi.org/10.1177/11782234241285411 |
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