%0 Journal Article
%T Therapeutic Implications of Targeting Energy Metabolism in Breast Cancer
%A Meena K. Sakharkar
%A Babita Shashni
%A Karun Sharma
%A Sarinder K. Dhillon
%A Prabhakar R. Ranjekar
%A Kishore R. Sakharkar
%J PPAR Research
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/109285
%X PPARs are ligand activated transcription factors. PPAR¦Ă agonists have been reported as a new and potentially efficacious treatment of inflammation, diabetes, obesity, cancer, AD, and schizophrenia. Since cancer cells show dysregulation of glycolysis they are potentially manageable through changes in metabolic environment. Interestingly, several of the genes involved in maintaining the metabolic environment and the central energy generation pathway are regulated or predicted to be regulated by PPAR¦Ă. The use of synthetic PPAR¦Ă ligands as drugs and their recent withdrawal/restricted usage highlight the lack of understanding of the molecular basis of these drugs, their off-target effects, and their network. These data further underscores the complexity of nuclear receptor signalling mechanisms. This paper will discuss the function and role of PPAR¦Ă in energy metabolism and cancer biology in general and its emergence as a promising therapeutic target in breast cancer. 1. Introduction The peroxisome proliferator-activated receptors (PPARs) are ligand activated transcription factors, belonging to the nuclear receptor superfamily, that control the expression of genes involved in organogenesis, inflammation, cell differentiation, proliferation, lipid, and carbohydrate metabolism [1, 2]. PPARs activated by their selected ligands, heterodimerizes and its receptor with the 9-cis-retinoic acid receptor, they then bind to peroxisome proliferator response elements (PPREs), specific sequences in their target genes. The consensus PPRE site consists of a direct repeat of the sequence AGGTCA separated by a single/double nucleotide, which is designated as DR-1 site/DR-2 site [3] (Figure 1). Each major isoforms of PPAR (PPAR¦Á, PPAR¦Â/¦Ä, and PPAR¦Ă), encoded by a different gene, performs different functions and exhibit different tissue localizations in many parts of the human body [4]. The peroxisome proliferator-activated receptor ¦Ă (PPAR¦Ă) is the most extensively studied subtype of the PPARs [5]. PPAR¦Ă is expressed in adipose tissue, colon, immune system, hematopoietic cells, and retina involved in lipid anabolism, adipocyte differentiation, control of inflammation, macrophage maturation, embryo implantation, and molecular targets of antidiabetic thiazolidinediones [6]. Its role in cancer development and potential as a target for cancer prevention and treatment strategies has been noted in recent years. Activation of PPAR¦Ă could possibly be an approach to induce differentiation in cells thereby inhibiting proliferation of a variety of cancers. This antiproliferative effect
%U http://www.hindawi.com/journals/ppar/2013/109285/