Induction of cell apoptosis by biliverdin reductase inhibitor in MCF-7 and MDA-MB-468 breast cancer cell lines
Biliverdin reductase, biliverdin and bilirubin are known as important components of cellular signaling pathways that play major roles in cell proliferation and apoptosis, although their physiological relevance is still under evaluation. This study was designed to investigate the expression and activ...
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| Format: | Article |
| Language: | English |
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IfADo - Leibniz Research Centre for Working Environment and Human Factors, Dortmund
2021-10-01
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| Series: | EXCLI Journal : Experimental and Clinical Sciences |
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| Online Access: | https://www.excli.de/index.php/excli/article/view/4069 |
| _version_ | 1797843503032565760 |
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| author | Seyedeh Zahra Shahrokhi Fatemeh Soghra Karami Tehrani Siamak Salami |
| author_facet | Seyedeh Zahra Shahrokhi Fatemeh Soghra Karami Tehrani Siamak Salami |
| author_sort | Seyedeh Zahra Shahrokhi |
| collection | DOAJ |
| description | Biliverdin reductase, biliverdin and bilirubin are known as important components of cellular signaling pathways that play major roles in cell proliferation and apoptosis, although their physiological relevance is still under evaluation. This study was designed to investigate the expression and activity of BVR-A and its apoptotic effect in the breast cancer cell lines, MCF‐7 and MDA‐MB‐468. The expression of BVR-A was examined by real‐time PCR and western blot analysis. Bilirubin concentration was measured by HPLC and molecular docking was performed to identify an appropriate inhibitor for BVR-A. To detect cell apoptosis, annexin V‐PI staining, caspase-3, -8, and -9 activities were evaluated. Cell viability was reduced by biliverdin, in a dose‐dependent manner, and an intrinsic apoptotic response occurred which was evidenced by caspase‐3 and -9 activities. The intra- and extracellular concentrations of bilirubin were higher in MCF-7 cells than those of MDA-MB-468 cells. The expression of BVR-A, at mRNA and protein levels, in MCF-7 was also higher than that of MDA-MB-468 cells. Treatment of both cell lines with biliverdin plus DTNB, a BVR-A inhibitor, increased the cell death significantly when compared with biliverdin alone. Using annexin V-PI staining and assessment of caspase‐3 activity, it was confirmed that biliverdin together with DTNB increases apoptosis in breast cancer cells. In conclusion, biliverdin has an important role in cell apoptosis and inhibition of biliverdin reductase increases the apoptotic effect of biliverdin. |
| first_indexed | 2024-04-09T17:06:18Z |
| format | Article |
| id | doaj.art-553b09d05e8a44398fda3230bbce6eee |
| institution | Directory Open Access Journal |
| issn | 1611-2156 |
| language | English |
| last_indexed | 2024-04-09T17:06:18Z |
| publishDate | 2021-10-01 |
| publisher | IfADo - Leibniz Research Centre for Working Environment and Human Factors, Dortmund |
| record_format | Article |
| series | EXCLI Journal : Experimental and Clinical Sciences |
| spelling | doaj.art-553b09d05e8a44398fda3230bbce6eee2023-04-20T13:35:19ZengIfADo - Leibniz Research Centre for Working Environment and Human Factors, DortmundEXCLI Journal : Experimental and Clinical Sciences1611-21562021-10-01201502151610.17179/excli2021-40693508Induction of cell apoptosis by biliverdin reductase inhibitor in MCF-7 and MDA-MB-468 breast cancer cell linesSeyedeh Zahra Shahrokhi0https://orcid.org/0000-0002-2028-5918Fatemeh Soghra Karami Tehrani1https://orcid.org/0000-0002-9768-946XSiamak Salami2https://orcid.org/0000-0003-0393-5058Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, IranDepartment of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. P.O. Box: 14115-331. E-mail: karamitf@modares.ac.irDepartment of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IranBiliverdin reductase, biliverdin and bilirubin are known as important components of cellular signaling pathways that play major roles in cell proliferation and apoptosis, although their physiological relevance is still under evaluation. This study was designed to investigate the expression and activity of BVR-A and its apoptotic effect in the breast cancer cell lines, MCF‐7 and MDA‐MB‐468. The expression of BVR-A was examined by real‐time PCR and western blot analysis. Bilirubin concentration was measured by HPLC and molecular docking was performed to identify an appropriate inhibitor for BVR-A. To detect cell apoptosis, annexin V‐PI staining, caspase-3, -8, and -9 activities were evaluated. Cell viability was reduced by biliverdin, in a dose‐dependent manner, and an intrinsic apoptotic response occurred which was evidenced by caspase‐3 and -9 activities. The intra- and extracellular concentrations of bilirubin were higher in MCF-7 cells than those of MDA-MB-468 cells. The expression of BVR-A, at mRNA and protein levels, in MCF-7 was also higher than that of MDA-MB-468 cells. Treatment of both cell lines with biliverdin plus DTNB, a BVR-A inhibitor, increased the cell death significantly when compared with biliverdin alone. Using annexin V-PI staining and assessment of caspase‐3 activity, it was confirmed that biliverdin together with DTNB increases apoptosis in breast cancer cells. In conclusion, biliverdin has an important role in cell apoptosis and inhibition of biliverdin reductase increases the apoptotic effect of biliverdin.https://www.excli.de/index.php/excli/article/view/4069biliverdin reductase-abreast cancer cell linescaspase activitymolecular dockinghigh-performance liquid chromatography |
| spellingShingle | Seyedeh Zahra Shahrokhi Fatemeh Soghra Karami Tehrani Siamak Salami Induction of cell apoptosis by biliverdin reductase inhibitor in MCF-7 and MDA-MB-468 breast cancer cell lines EXCLI Journal : Experimental and Clinical Sciences biliverdin reductase-a breast cancer cell lines caspase activity molecular docking high-performance liquid chromatography |
| title | Induction of cell apoptosis by biliverdin reductase inhibitor in MCF-7 and MDA-MB-468 breast cancer cell lines |
| title_full | Induction of cell apoptosis by biliverdin reductase inhibitor in MCF-7 and MDA-MB-468 breast cancer cell lines |
| title_fullStr | Induction of cell apoptosis by biliverdin reductase inhibitor in MCF-7 and MDA-MB-468 breast cancer cell lines |
| title_full_unstemmed | Induction of cell apoptosis by biliverdin reductase inhibitor in MCF-7 and MDA-MB-468 breast cancer cell lines |
| title_short | Induction of cell apoptosis by biliverdin reductase inhibitor in MCF-7 and MDA-MB-468 breast cancer cell lines |
| title_sort | induction of cell apoptosis by biliverdin reductase inhibitor in mcf 7 and mda mb 468 breast cancer cell lines |
| topic | biliverdin reductase-a breast cancer cell lines caspase activity molecular docking high-performance liquid chromatography |
| url | https://www.excli.de/index.php/excli/article/view/4069 |
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