Anticancer actions of PPARγ ligands: Current state and future perspectives in human lung cancer

Abstract

Peroxisome proliferator-activated receptors (PPARs) are ligand-dependent nuclear transcription factors and members of the nuclear receptor superfamily. Of the three PPARs identified to date (PPARγ, PPARβ/δ, and PPARα), PPARγ has been studied the most, in part because of the availability of PPARγ agonists (also known as PPARγ ligands) and its significant effects on the management of several human diseases including type 2 diabetes, metabolic syndrome, cardiovascular disease and cancers. PPARγ is expressed in many tumors including lung cancer, and its function has been linked to the process of lung cancer development, progression and metastasis. Studies performed in gynogenic and xenograft models of lung cancer showed decreased tumor growth and metastasis in animals treated with PPARγ ligands. Furthermore, data are emerging from retrospective clinical studies that suggest a protective role for PPARγ ligands on the incidence of lung cancer. This review summarizes the research being conducted in this area and focuses on the mechanisms and potential therapeutic effects of PPARγ ligands as a novel anti-lung cancer treatment strategy.

Geniposide inhibits non-small cell lung cancer cell migration and angiogenesis by regulating PPARγ/VEGF-A pathway

“…Genipin reduced the viability of NSCLC cell, H1299 (Zhang et al, 2015). Results in this study also established invasion (Han and Roman, 2010). VEGF was reported to be a downstream signaling of PPARγ in the regulation of cell apoptosis, proliferation, invasion, and angiogenesis (Han and Roman, 2010).…”

24-Methylenecycloartanyl Ferulate Induces PPAR-γ2 Mediated Regulation of Angiogenesis-Related Genes and Inhibits Akt/mTOR Signaling

“…Angiogenesis is the formation of new blood vessels and is a hallmark of tumor development and metastasis [23]. In particular, PPARγ targets a set of genes that have a critical impact on numerous diseases including angiogenesis and cancer [24,25]. PPARγ activation also inhibits angiogenesis by blocking ELR+CXC chemokine secretion, which is mediated through antagonizing NF-κB activation in non-small cell lung cancer (NSCLC) [26].…”

Microarray Analysis Identifies Pathways In Progression of Early Stage Lung Adenocarcinoma: The Importance of Focal Adhesion and ECM-Receptor Interactions

“…PPAR γ has been implicated as a tumour suppressor in NSCLC, and xenograft models of lung cancer show that it inhibits lung tumour cell proliferation and growth through a variety of metabolic activities. 42 Downregulation of the anti-tumour PPAR signalling may enhance the ability of NSCLC tumours to grow and metastasize. PPAR ligands are under development as potential therapeutic agents for lung cancer.…”