Therapeutic Implications of Targeting Energy Metabolism in Breast Cancer

Abstract

PPARs are ligand activated transcription factors. PPARγ 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 PPARγ. The use of synthetic PPARγ 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 PPARγ in energy metabolism and cancer biology in general and its emergence as a promising therapeutic target in breast cancer.

RETRACTED ARTICLE: Coffee component hydroxyl hydroquinone (HHQ) as a putative ligand for PPAR gamma and implications in breast cancer

“…This protein is involved in the mitochondrial apoptotic signaling pathway. The activation of the proapoptotic Bcl-2 family member Bax, induces permeabilization of the mitochondrial outer membrane and release of cytochrome c leading to caspase dependent apoptosis [ 42 , 43 ]. Together, these data corroborate with our previous results and demonstrate that there is disruption in mitochondrial potential, permeability and functioning upon PPARγ activation by HHQ.…”

Blocking PPARγ interaction facilitates Nur77 interdiction of fatty acid uptake and suppresses breast cancer progression

“…Analysis by mass spectrometry of Nur77 immunoprecipitates from the nucleus of MCF-7 cells also indicated that nuclear receptor PPARγ, known for its role in regulating lipid metabolism, such as lipid uptake (28,29), could be a novel Nur77 binding protein (SI Appendix, Fig. S4B and Dataset S1).…”

Emerging functional roles of nuclear receptors in breast cancer

“…Recent studies have also suggested an involvement of PPARG and energy metabolism in breast cancer. Firstly, several genes controlling the glycolytic pathways are found to have peroxisome proliferator response element (PPRE) suggesting their regulation by PPARs (Sakharkar et al 2013). Secondly, overexpression of PPARG in fibroblasts increased the production of l-lactate and mitochondrial dysfunction.…”