Induction of cell apoptosis by biliverdin reductase inhibitor in MCF-7 and MDA-MB-468 breast cancer cell lines

Experimental and in silico studies

Authors

  • Seyedeh Zahra Shahrokhi Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran https://orcid.org/0000-0002-2028-5918
  • Fatemeh Soghra Karami Tehrani Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. P.O. Box: 14115-331. E-mail: karamitf@modares.ac.ir https://orcid.org/0000-0002-9768-946X
  • Siamak Salami Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran https://orcid.org/0000-0003-0393-5058

DOI:

https://doi.org/10.17179/excli2021-4069

Keywords:

biliverdin reductase-A, breast cancer cell lines, caspase activity, molecular docking, high-performance liquid chromatography

Abstract

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.

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Published

2021-10-21

How to Cite

Shahrokhi, S. Z., Karami Tehrani, F. S., & Salami, S. (2021). Induction of cell apoptosis by biliverdin reductase inhibitor in MCF-7 and MDA-MB-468 breast cancer cell lines: Experimental and in silico studies. EXCLI Journal, 20, 1502–1516. https://doi.org/10.17179/excli2021-4069

Issue

Vol. 20 (2021)

Section

Original articles

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Copyright (c) 2021 Seyedeh Zahra Shahrokhi, Fatemeh Soghra Karami Tehrani, Siamak Salami

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