Regucalcin ameliorates doxorubicin-induced cytotoxicity in Cos-7 kidney cells and translocates from the nucleus to the mitochondria

Author:

Mohammed Noor A.12,Hakeem Israa J.1,Hodges Nikolas1,Michelangeli Francesco3ORCID

Affiliation:

1. School of Biosciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, U.K.

2. Department of Biology, College of Science, University of Duhok, Zakho Street 38, 1006 AJ, Duhok, PO Box 78, Iraq

3. Faculty of Medicine, Dentistry and Life Sciences, University of Chester, Parkgate Rd, Chester, CH1 4BJ, U.K.

Abstract

Abstract Doxorubicin (DOX) is a potent anticancer drug, which can have unwanted side-effects such as cardiac and kidney toxicity. A detailed investigation was undertaken of the acute cytotoxic mechanisms of DOX on kidney cells, using Cos-7 cells as kidney cell model. Cos-7 cells were exposed to DOX for a period of 24 h over a range of concentrations, and the LC50 was determined to be 7 µM. Further investigations showed that cell death was mainly via apoptosis involving Ca2+ and caspase 9, in addition to autophagy. Regucalcin (RGN), a cytoprotective protein found mainly in liver and kidney tissues, was overexpressed in Cos-7 cells and shown to protect against DOX-induced cell death. Subcellular localization studies in Cos-7 cells showed RGN to be strongly correlated with the nucleus. However, upon treatment with DOX for 4 h, which induced membrane blebbing in some cells, the localization appeared to be correlated more with the mitochondria in these cells. It is yet to be determined whether this translocation is part of the cytoprotective mechanism or a consequence of chemically induced cell stress.

Publisher

Portland Press Ltd.

Subject

Cell Biology,Molecular Biology,Biochemistry,Biophysics

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