Regucalcin protects HEPG2 cells from Doxorubicin-induced apoptosis and autophagy
Noor Mohammed, Frank Michelangeli and Nikolas Hodges
University of Birmingham School of Bioscience, B15 2TT
: J Pharm Drug Deliv Res
Abstract
Regucalcin (RGN) is a cytosolic Ca2+-binding protein that was discovered in 1978 and is known to be a multi-functional
protein involved in number of cellular processes including – calcium homeostasis by regulating Ca²+ binding protein activity
such as Ca2+-ATPases, calmodulinkinase and PKC. This protein is mostly found in liver and kidney tissues. Furthermore, RGN
also plays a defence role in Ca2+-mediated stress protection and apoptosis. Doxorubicin (DOX) is a potent anti-cancer drug
that is used either in isolation or in combination with other drugs for treating variety of cancers. Several studies have shown
that DOX induces p53 activation leading to apoptosis in both normal and tumourendothelial cardiomyocytes cells; by causing
cytochrome c release from the mitochondria, resulting in caspase 3 activation and induction of apoptosis. Moreover, this drug
has the ability to damage DNA by producing reactive oxygen species. A major problem of DOX treatment is that it is highly
cardio- and hepato-toxic.
In the current study we have investigated the molecular mechanisms of DOX-induced hepatic cell death and show that
DOX can induce cell death in human HepG2 liver cells through a number of different mechanisms including; apoptosis, DNA
damage and autophagy. However, necrosis does not appear to be involved in this process. Furthermore, over-expression of
RGN in HepG2 cells was found to protect against the toxicity by DOX. Therefore increased expression of RGN in the liver
could be a mechanism for protection against DOX-induced toxicity.
Biography
Noor has completed her master degree(MSc) in Histologyon March2010 from university of Duhok (Kurdistan Region Government of Iraq) and has published her master thesis as two papers in local university journal. Noor worked as anassistant lecturer in biology department, university of Duhoksince 2010then she started her PhD on September 2013 focusing on the mechanism effect of chemotherapy drugs on liver and kidney cell line.
Email: Nkamil@kfu.edu.sa
