Carvedilol As A Potential Chemotherapeutic And Cancer Preventive Agent Through Its Inhibition Of Parp-1

Carvedilol is an established anti-hypertensive medication used as one of the cornerstones of congestive heart failure. In addition to its cardiac remodeling properties, recent interest has been shown in the field of cancer mutagenesis. Inhibition of various proteins involved in proliferation pathways in cancer formation has shown potential therapeutic applications in protecting against apoptosis. Various clinical trials have recently been employed to study potential inhibitors of poly (ADP-ribose) polymerase 1, a well-known protein involved in cancer mutagenesis. Our study suggests a potential inhibitory interaction with polymerase 1and Carvedilol.By using virtual screening target software, we hope to identify a potential pharmacological interaction between Carvedilol and various well known cancer genes, which can serve as possible therapeutic targets and potential chemo-preventative agents.We used PyRx, which is a virtual screening and docking software program, to screen proteins known to be involved in DNA repair, cancer prevention, and programmed cell death pathways and measure their binding affinities with Carvedilol.Among the various proteins tested with our virtual screening program, Carvedilol showed the highest binding affinity of -8.7 kcal/mol, to polymerase 1as well as with the receptor tyrosineprotein kinase erb-2, (HER2/neu), often found frequently in breast cancer (-8.3 kcal/mol) and also with the serine protein kinase ATM protein, involved in Ataxia Telangiectasia with a high binding affinity of -8.8 kcal/mol.Although numerous anti-cancer mechanisms have been postulated and appropriate pharmaceutical agents have been designed which have decreased mortality, unwanted toxicity and cost has remained a limiting factor. Recent studies have focused on particular cancer mutagenesis pathways such as the role of polymerase 1 and proliferation in certain cancers. Our studies suggest a significant binding and inhibition of polymerase 1 with Carvedilol. This presents a novel and potential therapeutic role as a cost effective and readily available cancer treatment as well as possible chemo-preventative medication in certain cancers with little or no effective treatments.