Benzyl Isothiocyanate Induces Apoptosis and Inhibits Tumor Growth in Canine Mammary Carcinoma via Downregulation of the Cyclin B1/Cdk1 Pathway
Background: Canine mammary carcinoma is common in female dogs, and its poor prognosis remains a serious clinical challenge, especially in developing countries. Benzyl isothiocyanate (BITC) has attracted great interest because of its inhibitory effect against tumor activity. However, its effect and t...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-11-01
|
| Series: | Frontiers in Veterinary Science |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fvets.2020.580530/full |
| _version_ | 1818405707444125696 |
|---|---|
| author | Nan Cheng Hongxiu Diao Zhaoyan Lin Jiafeng Gao Ying Zhao Weijiao Zhang Qi Wang Jiahao Lin Di Zhang Yipeng Jin Yongping Bao Degui Lin |
| author_facet | Nan Cheng Hongxiu Diao Zhaoyan Lin Jiafeng Gao Ying Zhao Weijiao Zhang Qi Wang Jiahao Lin Di Zhang Yipeng Jin Yongping Bao Degui Lin |
| author_sort | Nan Cheng |
| collection | DOAJ |
| description | Background: Canine mammary carcinoma is common in female dogs, and its poor prognosis remains a serious clinical challenge, especially in developing countries. Benzyl isothiocyanate (BITC) has attracted great interest because of its inhibitory effect against tumor activity. However, its effect and the underlying mechanisms of action in canine mammary cancer are not well-understood. Here, we show that BITC suppresses mammary tumor growth, both in vivo and in vitro, and reveal some of the potential mechanisms involved.Methods: The effect of BITC on canine mammary cancer was evaluated on CIPp and CMT-7364, canine mammary carcinoma lines. The cell lines were treated with BITC and then subjected to wound healing and invasion assays. Cell cycles and apoptosis were measured using flow cytometry; TUNEL assay; immunohistochemistry (IHC) for caspase 3, caspase 9, and cyclin D1; hematoxylin and eosin (H&E) staining; and/or quantitative polymerase chain reaction (qPCR).Results: BITC showed a strong suppressive effect in both CIPp and CMT-7364 cells by inhibiting cell growth in vitro; these effects were both dose- and time-dependent. BITC also inhibited migration and invasion of CIPp and CMT-7364 cells. BITC induced G2 arrest and apoptosis, decreasing tumor growth in nude mice by downregulation of cyclin B1 and Cdk1 expression.Conclusion: BITC suppressed both invasion and migration of CIPp and CMT-7364 cells and induced apoptosis. BITC inhibited canine mammary tumor growth by suppressing cyclinB1 and Cdk1 expression in nude mice. |
| first_indexed | 2024-12-14T09:00:19Z |
| format | Article |
| id | doaj.art-d8b05acd9f59414f8fd753af48e1fe99 |
| institution | Directory Open Access Journal |
| issn | 2297-1769 |
| language | English |
| last_indexed | 2024-12-14T09:00:19Z |
| publishDate | 2020-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Veterinary Science |
| spelling | doaj.art-d8b05acd9f59414f8fd753af48e1fe992022-12-21T23:08:50ZengFrontiers Media S.A.Frontiers in Veterinary Science2297-17692020-11-01710.3389/fvets.2020.580530580530Benzyl Isothiocyanate Induces Apoptosis and Inhibits Tumor Growth in Canine Mammary Carcinoma via Downregulation of the Cyclin B1/Cdk1 PathwayNan Cheng0Hongxiu Diao1Zhaoyan Lin2Jiafeng Gao3Ying Zhao4Weijiao Zhang5Qi Wang6Jiahao Lin7Di Zhang8Yipeng Jin9Yongping Bao10Degui Lin11Department of Veterinary Clinical Science, College of Veterinary Medicine, China Agricultural University, Beijing, ChinaDepartment of Veterinary Clinical Science, College of Veterinary Medicine, China Agricultural University, Beijing, ChinaDepartment of Veterinary Clinical Science, College of Veterinary Medicine, China Agricultural University, Beijing, ChinaDepartment of Veterinary Clinical Science, College of Veterinary Medicine, China Agricultural University, Beijing, ChinaDepartment of Veterinary Clinical Science, College of Veterinary Medicine, China Agricultural University, Beijing, ChinaFaculty of Medicine and Health, Norwich Medical School, University of East Anglia, Norwich, United KingdomFaculty of Medicine and Health, Norwich Medical School, University of East Anglia, Norwich, United KingdomDepartment of Veterinary Clinical Science, College of Veterinary Medicine, China Agricultural University, Beijing, ChinaDepartment of Veterinary Clinical Science, College of Veterinary Medicine, China Agricultural University, Beijing, ChinaDepartment of Veterinary Clinical Science, College of Veterinary Medicine, China Agricultural University, Beijing, ChinaFaculty of Medicine and Health, Norwich Medical School, University of East Anglia, Norwich, United KingdomDepartment of Veterinary Clinical Science, College of Veterinary Medicine, China Agricultural University, Beijing, ChinaBackground: Canine mammary carcinoma is common in female dogs, and its poor prognosis remains a serious clinical challenge, especially in developing countries. Benzyl isothiocyanate (BITC) has attracted great interest because of its inhibitory effect against tumor activity. However, its effect and the underlying mechanisms of action in canine mammary cancer are not well-understood. Here, we show that BITC suppresses mammary tumor growth, both in vivo and in vitro, and reveal some of the potential mechanisms involved.Methods: The effect of BITC on canine mammary cancer was evaluated on CIPp and CMT-7364, canine mammary carcinoma lines. The cell lines were treated with BITC and then subjected to wound healing and invasion assays. Cell cycles and apoptosis were measured using flow cytometry; TUNEL assay; immunohistochemistry (IHC) for caspase 3, caspase 9, and cyclin D1; hematoxylin and eosin (H&E) staining; and/or quantitative polymerase chain reaction (qPCR).Results: BITC showed a strong suppressive effect in both CIPp and CMT-7364 cells by inhibiting cell growth in vitro; these effects were both dose- and time-dependent. BITC also inhibited migration and invasion of CIPp and CMT-7364 cells. BITC induced G2 arrest and apoptosis, decreasing tumor growth in nude mice by downregulation of cyclin B1 and Cdk1 expression.Conclusion: BITC suppressed both invasion and migration of CIPp and CMT-7364 cells and induced apoptosis. BITC inhibited canine mammary tumor growth by suppressing cyclinB1 and Cdk1 expression in nude mice.https://www.frontiersin.org/articles/10.3389/fvets.2020.580530/fullBITCapoptosiscyclin B1canine mammary tumorCdk1 |
| spellingShingle | Nan Cheng Hongxiu Diao Zhaoyan Lin Jiafeng Gao Ying Zhao Weijiao Zhang Qi Wang Jiahao Lin Di Zhang Yipeng Jin Yongping Bao Degui Lin Benzyl Isothiocyanate Induces Apoptosis and Inhibits Tumor Growth in Canine Mammary Carcinoma via Downregulation of the Cyclin B1/Cdk1 Pathway Frontiers in Veterinary Science BITC apoptosis cyclin B1 canine mammary tumor Cdk1 |
| title | Benzyl Isothiocyanate Induces Apoptosis and Inhibits Tumor Growth in Canine Mammary Carcinoma via Downregulation of the Cyclin B1/Cdk1 Pathway |
| title_full | Benzyl Isothiocyanate Induces Apoptosis and Inhibits Tumor Growth in Canine Mammary Carcinoma via Downregulation of the Cyclin B1/Cdk1 Pathway |
| title_fullStr | Benzyl Isothiocyanate Induces Apoptosis and Inhibits Tumor Growth in Canine Mammary Carcinoma via Downregulation of the Cyclin B1/Cdk1 Pathway |
| title_full_unstemmed | Benzyl Isothiocyanate Induces Apoptosis and Inhibits Tumor Growth in Canine Mammary Carcinoma via Downregulation of the Cyclin B1/Cdk1 Pathway |
| title_short | Benzyl Isothiocyanate Induces Apoptosis and Inhibits Tumor Growth in Canine Mammary Carcinoma via Downregulation of the Cyclin B1/Cdk1 Pathway |
| title_sort | benzyl isothiocyanate induces apoptosis and inhibits tumor growth in canine mammary carcinoma via downregulation of the cyclin b1 cdk1 pathway |
| topic | BITC apoptosis cyclin B1 canine mammary tumor Cdk1 |
| url | https://www.frontiersin.org/articles/10.3389/fvets.2020.580530/full |
| work_keys_str_mv | AT nancheng benzylisothiocyanateinducesapoptosisandinhibitstumorgrowthincaninemammarycarcinomaviadownregulationofthecyclinb1cdk1pathway AT hongxiudiao benzylisothiocyanateinducesapoptosisandinhibitstumorgrowthincaninemammarycarcinomaviadownregulationofthecyclinb1cdk1pathway AT zhaoyanlin benzylisothiocyanateinducesapoptosisandinhibitstumorgrowthincaninemammarycarcinomaviadownregulationofthecyclinb1cdk1pathway AT jiafenggao benzylisothiocyanateinducesapoptosisandinhibitstumorgrowthincaninemammarycarcinomaviadownregulationofthecyclinb1cdk1pathway AT yingzhao benzylisothiocyanateinducesapoptosisandinhibitstumorgrowthincaninemammarycarcinomaviadownregulationofthecyclinb1cdk1pathway AT weijiaozhang benzylisothiocyanateinducesapoptosisandinhibitstumorgrowthincaninemammarycarcinomaviadownregulationofthecyclinb1cdk1pathway AT qiwang benzylisothiocyanateinducesapoptosisandinhibitstumorgrowthincaninemammarycarcinomaviadownregulationofthecyclinb1cdk1pathway AT jiahaolin benzylisothiocyanateinducesapoptosisandinhibitstumorgrowthincaninemammarycarcinomaviadownregulationofthecyclinb1cdk1pathway AT dizhang benzylisothiocyanateinducesapoptosisandinhibitstumorgrowthincaninemammarycarcinomaviadownregulationofthecyclinb1cdk1pathway AT yipengjin benzylisothiocyanateinducesapoptosisandinhibitstumorgrowthincaninemammarycarcinomaviadownregulationofthecyclinb1cdk1pathway AT yongpingbao benzylisothiocyanateinducesapoptosisandinhibitstumorgrowthincaninemammarycarcinomaviadownregulationofthecyclinb1cdk1pathway AT deguilin benzylisothiocyanateinducesapoptosisandinhibitstumorgrowthincaninemammarycarcinomaviadownregulationofthecyclinb1cdk1pathway |