New fluorobenzamidine exerts antitumor activity against breast cancer in mice via pro-apoptotic activity
Abstract Background Breast cancer is one of the leading causes of cancer-related morbidities. The present study aimed to evaluate the efficacy of bithiophene-fluorobenzamidine (BFB) against breast cancer induced by 7,12-dimethylbenz(a)anthracene (DMBA) in female Swiss mice and reveal the underlining...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Springer
2022-09-01
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| Series: | Discover Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1007/s12672-022-00554-6 |
| _version_ | 1797994904208539648 |
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| author | AbdelRahman B. Saleh Nagwa H. Hassan Mohamed A. Ismail Wael M. El-Sayed |
| author_facet | AbdelRahman B. Saleh Nagwa H. Hassan Mohamed A. Ismail Wael M. El-Sayed |
| author_sort | AbdelRahman B. Saleh |
| collection | DOAJ |
| description | Abstract Background Breast cancer is one of the leading causes of cancer-related morbidities. The present study aimed to evaluate the efficacy of bithiophene-fluorobenzamidine (BFB) against breast cancer induced by 7,12-dimethylbenz(a)anthracene (DMBA) in female Swiss mice and reveal the underlining mechanisms. Methods The mice were randomly divided into five groups; control, BFB-treated group, DMBA-treated group, and the last two groups received DMBA then tamoxifen or BFB. Results BFB reduced the tumor incidence by ~ 88% versus 30% after TAM. DMBA significantly increased the expression of CDK1 and HER2 and reduced the expression of p53, p21 (CDKN1A), ESR-α, and CAS3. BFB caused significant down-regulation of CDK1 and HER2 and upregulation of p53, p21, ESR-α, and CAS3. In the DMBA-treated mice, cancerous cells metastasized to several organs. This was prevented by the administration of BFB. The antimetastatic and proapoptotic activities were confirmed in MCF7 cells in vitro by the wound healing and annexin V assays, respectively. Kaplan–Meier analysis showed that the BFB increased survival. In the DMBA group, tumors showed invasive carcinoma of grade III with central necrosis, polymorphism, mitotic activity, and numerous newly formed ductules, and colloidal mucinous secretions within adenoid cysts. BFB administration restored the normal structure of the mammary glands. Conclusion Taken together, BFB has antitumor, pro-apoptotic, and anti-metastatic activities against breast cancer in mice and therefore, it merits further investigations. |
| first_indexed | 2024-04-11T09:51:56Z |
| format | Article |
| id | doaj.art-87740a3d67494dd792161e072f03c787 |
| institution | Directory Open Access Journal |
| issn | 2730-6011 |
| language | English |
| last_indexed | 2024-04-11T09:51:56Z |
| publishDate | 2022-09-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj.art-87740a3d67494dd792161e072f03c7872022-12-22T04:30:45ZengSpringerDiscover Oncology2730-60112022-09-0113111410.1007/s12672-022-00554-6New fluorobenzamidine exerts antitumor activity against breast cancer in mice via pro-apoptotic activityAbdelRahman B. Saleh0Nagwa H. Hassan1Mohamed A. Ismail2Wael M. El-Sayed3Department of Zoology, Faculty of Science, Ain Shams UniversityDepartment of Zoology, Faculty of Science, Ain Shams UniversityDepartment of Chemistry, Faculty of Science, Mansoura UniversityDepartment of Zoology, Faculty of Science, Ain Shams UniversityAbstract Background Breast cancer is one of the leading causes of cancer-related morbidities. The present study aimed to evaluate the efficacy of bithiophene-fluorobenzamidine (BFB) against breast cancer induced by 7,12-dimethylbenz(a)anthracene (DMBA) in female Swiss mice and reveal the underlining mechanisms. Methods The mice were randomly divided into five groups; control, BFB-treated group, DMBA-treated group, and the last two groups received DMBA then tamoxifen or BFB. Results BFB reduced the tumor incidence by ~ 88% versus 30% after TAM. DMBA significantly increased the expression of CDK1 and HER2 and reduced the expression of p53, p21 (CDKN1A), ESR-α, and CAS3. BFB caused significant down-regulation of CDK1 and HER2 and upregulation of p53, p21, ESR-α, and CAS3. In the DMBA-treated mice, cancerous cells metastasized to several organs. This was prevented by the administration of BFB. The antimetastatic and proapoptotic activities were confirmed in MCF7 cells in vitro by the wound healing and annexin V assays, respectively. Kaplan–Meier analysis showed that the BFB increased survival. In the DMBA group, tumors showed invasive carcinoma of grade III with central necrosis, polymorphism, mitotic activity, and numerous newly formed ductules, and colloidal mucinous secretions within adenoid cysts. BFB administration restored the normal structure of the mammary glands. Conclusion Taken together, BFB has antitumor, pro-apoptotic, and anti-metastatic activities against breast cancer in mice and therefore, it merits further investigations.https://doi.org/10.1007/s12672-022-00554-6BithiopheneTamoxifenApoptosisCDK1ESR |
| spellingShingle | AbdelRahman B. Saleh Nagwa H. Hassan Mohamed A. Ismail Wael M. El-Sayed New fluorobenzamidine exerts antitumor activity against breast cancer in mice via pro-apoptotic activity Discover Oncology Bithiophene Tamoxifen Apoptosis CDK1 ESR |
| title | New fluorobenzamidine exerts antitumor activity against breast cancer in mice via pro-apoptotic activity |
| title_full | New fluorobenzamidine exerts antitumor activity against breast cancer in mice via pro-apoptotic activity |
| title_fullStr | New fluorobenzamidine exerts antitumor activity against breast cancer in mice via pro-apoptotic activity |
| title_full_unstemmed | New fluorobenzamidine exerts antitumor activity against breast cancer in mice via pro-apoptotic activity |
| title_short | New fluorobenzamidine exerts antitumor activity against breast cancer in mice via pro-apoptotic activity |
| title_sort | new fluorobenzamidine exerts antitumor activity against breast cancer in mice via pro apoptotic activity |
| topic | Bithiophene Tamoxifen Apoptosis CDK1 ESR |
| url | https://doi.org/10.1007/s12672-022-00554-6 |
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