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

Abstract

Doxorubicin (DOX) is a potent anti-cancer 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 hours over a range of concentrations and the LC50 was determined to be 7µM. 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 hours, 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.

Liraglutide Pretreatment Does Not Improve Acute Doxorubicin-Induced Cardiotoxicity in Rats

“…Doxorubicin is one of the most studied chemotherapy drugs because of its high effectiveness in treating several types of cancer, and especially, in reason of the severe side effects caused in systems such as the heart [ 16 , 17 , 18 , 19 ], intestines [ 20 , 21 , 22 ], kidney [ 23 , 24 , 25 , 26 ], liver [ 27 , 28 ], skeletal muscles [ 29 , 30 , 31 , 32 ], and bone marrow [ 33 , 34 ]. The heart is the most studied organ due to its potential development of heart failure, a chronic, limiting, and high-mortality condition [ 35 ].…”

Phytochemical investigation and biological studies of Euphorbia tithymaloides L. family Euphorbiaceae

“…The IC₅₀ values of HepG2, MCF-7, PC-3 and HCT-116 are shown in (Table 5). Doxorubicin (Tacar et al, 2013); (Mohamed et al, 2022) was used as a positive control drug in this assay. Compound 6 isolated from the CH₂Cl₂ extract of the stem was active against all tested cell lines.…”