In vitro anti-proliferative effect of capecitabine (Xeloda) combined with mocetinostat (MGCD0103) in 4T1 breast cancer cell line by immunoblotting
Objective(s): Mouse breast cancer cell line 4T1 can accurately mimic the response to immune receptors and targeting therapeutic agents. Combined therapy has emerged as an important strategy with reduced side effects and maximum therapeutic effect. Mocetinostat (MGCD0103) is one of the members of Cla...
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| Format: | Article |
| Language: | English |
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Mashhad University of Medical Sciences
2021-11-01
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| Series: | Iranian Journal of Basic Medical Sciences |
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| Online Access: | https://ijbms.mums.ac.ir/article_18942_3a210512b2bdfdd500f264801c1231c0.pdf |
| _version_ | 1818773610296246272 |
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| author | Hacer Kaya Cakır Onur Eroglu |
| author_facet | Hacer Kaya Cakır Onur Eroglu |
| author_sort | Hacer Kaya Cakır |
| collection | DOAJ |
| description | Objective(s): Mouse breast cancer cell line 4T1 can accurately mimic the response to immune receptors and targeting therapeutic agents. Combined therapy has emerged as an important strategy with reduced side effects and maximum therapeutic effect. Mocetinostat (MGCD0103) is one of the members of Class I Histone Deacetylase Inhibitors (HDACi) and its mechanism of action has not been defined, yet. Capecitabine (Xeloda) is an antimetabolite and currently is widely utilized to treat a wide range of solid tumors. The aim of this study was to investigate the effects of the capecitabine, mocetinostat and their combined application on the 4T1 cell line. Materials and Methods: The effects of combined administration of mocetinostat and capecitabine on 4T1 cells were investigated by cell viability and migration assays, apoptosis analysis, and Western blotting technique.Results: The concentrations of drugs that give a half-maximal response (IC50) were detected for capecitabine (1700 µM), mocetinostat (3,125 µM), and 50 µM Capecitabine+1,5 µM Mocetinostat for 48 hr. In capecitabine+mocetinostat combine group, we observed that cell migration decreased, DNA fragmentation increased compared to the control group. capecitabine + mocetinostat group induced apoptosis by decreasing Bcl-2, PI3K, Akt, c-myc protein levels, while increasing Bax, Caspase-3, PTEN, cleaved-PARP, Caspase-7, Caspase-9, p53, cleaved-Cas-9 protein levels in 4T1 cells. Conclusion: Capecitabine and mocetinostat played a toxic role through inducing apoptosis on 4T1 cancer cells in a time- and concentration-dependent manner. These results showed that combined therapy with low concentrations were detected to be more effective than that with high-concentration alone drug treatment. |
| first_indexed | 2024-12-18T10:27:59Z |
| format | Article |
| id | doaj.art-2ba6994484584ce4aa8d5aa7cab47d59 |
| institution | Directory Open Access Journal |
| issn | 2008-3866 2008-3874 |
| language | English |
| last_indexed | 2024-12-18T10:27:59Z |
| publishDate | 2021-11-01 |
| publisher | Mashhad University of Medical Sciences |
| record_format | Article |
| series | Iranian Journal of Basic Medical Sciences |
| spelling | doaj.art-2ba6994484584ce4aa8d5aa7cab47d592022-12-21T21:10:56ZengMashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-38662008-38742021-11-0124111515152210.22038/ijbms.2021.58393.1297118942In vitro anti-proliferative effect of capecitabine (Xeloda) combined with mocetinostat (MGCD0103) in 4T1 breast cancer cell line by immunoblottingHacer Kaya Cakır0Onur Eroglu1Department of Molecular Biology and Genetics, Faculty of Science and Letters, Bilecik Seyh Edebali University, Bilecik, TurkeyDepartment of Molecular Biology and Genetics, Faculty of Science and Letters, Bilecik Seyh Edebali University, Bilecik, TurkeyObjective(s): Mouse breast cancer cell line 4T1 can accurately mimic the response to immune receptors and targeting therapeutic agents. Combined therapy has emerged as an important strategy with reduced side effects and maximum therapeutic effect. Mocetinostat (MGCD0103) is one of the members of Class I Histone Deacetylase Inhibitors (HDACi) and its mechanism of action has not been defined, yet. Capecitabine (Xeloda) is an antimetabolite and currently is widely utilized to treat a wide range of solid tumors. The aim of this study was to investigate the effects of the capecitabine, mocetinostat and their combined application on the 4T1 cell line. Materials and Methods: The effects of combined administration of mocetinostat and capecitabine on 4T1 cells were investigated by cell viability and migration assays, apoptosis analysis, and Western blotting technique.Results: The concentrations of drugs that give a half-maximal response (IC50) were detected for capecitabine (1700 µM), mocetinostat (3,125 µM), and 50 µM Capecitabine+1,5 µM Mocetinostat for 48 hr. In capecitabine+mocetinostat combine group, we observed that cell migration decreased, DNA fragmentation increased compared to the control group. capecitabine + mocetinostat group induced apoptosis by decreasing Bcl-2, PI3K, Akt, c-myc protein levels, while increasing Bax, Caspase-3, PTEN, cleaved-PARP, Caspase-7, Caspase-9, p53, cleaved-Cas-9 protein levels in 4T1 cells. Conclusion: Capecitabine and mocetinostat played a toxic role through inducing apoptosis on 4T1 cancer cells in a time- and concentration-dependent manner. These results showed that combined therapy with low concentrations were detected to be more effective than that with high-concentration alone drug treatment.https://ijbms.mums.ac.ir/article_18942_3a210512b2bdfdd500f264801c1231c0.pdfapoptosisbreast neoplasmsdrug synergismcapecitabinehistone deacetylase inhibitors |
| spellingShingle | Hacer Kaya Cakır Onur Eroglu In vitro anti-proliferative effect of capecitabine (Xeloda) combined with mocetinostat (MGCD0103) in 4T1 breast cancer cell line by immunoblotting Iranian Journal of Basic Medical Sciences apoptosis breast neoplasms drug synergism capecitabine histone deacetylase inhibitors |
| title | In vitro anti-proliferative effect of capecitabine (Xeloda) combined with mocetinostat (MGCD0103) in 4T1 breast cancer cell line by immunoblotting |
| title_full | In vitro anti-proliferative effect of capecitabine (Xeloda) combined with mocetinostat (MGCD0103) in 4T1 breast cancer cell line by immunoblotting |
| title_fullStr | In vitro anti-proliferative effect of capecitabine (Xeloda) combined with mocetinostat (MGCD0103) in 4T1 breast cancer cell line by immunoblotting |
| title_full_unstemmed | In vitro anti-proliferative effect of capecitabine (Xeloda) combined with mocetinostat (MGCD0103) in 4T1 breast cancer cell line by immunoblotting |
| title_short | In vitro anti-proliferative effect of capecitabine (Xeloda) combined with mocetinostat (MGCD0103) in 4T1 breast cancer cell line by immunoblotting |
| title_sort | in vitro anti proliferative effect of capecitabine xeloda combined with mocetinostat mgcd0103 in 4t1 breast cancer cell line by immunoblotting |
| topic | apoptosis breast neoplasms drug synergism capecitabine histone deacetylase inhibitors |
| url | https://ijbms.mums.ac.ir/article_18942_3a210512b2bdfdd500f264801c1231c0.pdf |
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