Pharmacology and Ethnopharmacology

Biography

Biography: Noor Mohammed

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, calmodulin kinase 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 tumour endothelial 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.