PPAR-γ Modulators as Current and Potential Cancer Treatments

Abstract

Worldwide, cancer has become one of the leading causes of mortality. Peroxisome Proliferator-Activated Receptors (PPARs) is a family of critical sensors of lipids as well as regulators of diverse metabolic pathways. They are also equipped with the capability to promote eNOS activation, regulate immunity and inflammation response. Aside from the established properties, emerging discoveries are also made in PPAR’s functions in the cancer field. All considerations are given, there exists great potential in PPAR modulators which may hold in the management of cancers. In particular, PPAR-γ, the most expressed subtype in adipose tissues with two isoforms of different tissue distribution, has been proven to be able to inhibit cell proliferation, induce cell cycle termination and apoptosis of multiple cancer cells, promote intercellular adhesion, and cripple the inflamed state of tumor microenvironment, both on transcriptional and protein level. However, despite the multi-functionalities, the safety of PPAR-γ modulators is still of clinical concern in terms of dosage, drug interactions, cancer types and stages, etc. This review aims to consolidate the functions of PPAR-γ, the current and potential applications of PPAR-γ modulators, and the challenges in applying PPAR-γ modulators to cancer treatment, in both laboratory and clinical settings. We sincerely hope to provide a comprehensive perspective on the prospect of PPAR-γ applicability in the field of cancer treatment.

Evaluation of the expression pattern and diagnostic value of PPARγ in malignant and benign primary bone tumors

“…Although the results of in-vitro studies on osteosarcoma cells favor the role of tumor suppressor of PPARγ [ 36 ], data of the current study showed the enhanced level of PPARγ in tumors with more severity. Rationally activation of PPARγ is required for glucose and lipid metabolism to meet the high demands of energy for cancer cell growth, invasion and migration [ 13 ]. Considering the fact that mRNA expression might not end up in protein translation, therefore, the simultaneous study of PPARγ mRNA and protein in this study showed a more complete picture of the status of PPARγ.…”

“…The tight linkage between PPARγ and cancer has attributed to the multi functions of PPAR γ in metabolic reprogramming of cancer cells, tumor cell-associated secretions, tumor microenvironment and adaptations also immune response [ 11 ], however, the oncogenic or tumor suppressive role of PPARγ is controversial and dependent on the tumor cell type, origin, individual-specific manner and a dose concentration [ 12 ]. In support of the tumoricidal effect of PPARγ, it was shown that its activation is associated with overexpression of vascular endothelial growth factor A (VEGF-A) and vimentin, as the major component of cell migration and angiogenesis [ 13 ]. While multiple lines of evidence highlighted the tumor suppressive role of PPARγ in regulating cancer cell growth and PPARγ agonists induced different types of programmed cell death pathways in cancer cells [ 14 ].…”

Unlaid Eggs: Ovarian Damage after Low-Dose Radiation

“…Bottom: Development from PMF pool to young adulthood in mice and humans and human folliculogenesis and detail in PMF pool in humans at birth. Adapted from [ 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 ].…”

Peroxiporins Are Induced upon Oxidative Stress Insult and Are Associated with Oxidative Stress Resistance in Colon Cancer Cell Lines

“…Cancer growth is supported by changes in the cell’s metabolic pathways, which are caused either by the abovementioned genetic instability or by changes in transcription factors. Peroxisome proliferator-activated receptors (PPAR) are a group of ligand-activated transcription factors that regulate lipid metabolism, immune response, and glucose metabolism [ 9 ]. PPARγ is part of the PPAR family, mostly present in adipose tissue [ 10 ].…”

“…PPARγ is part of the PPAR family, mostly present in adipose tissue [ 10 ]. Dysregulation of PPARγ in cancer is observed, with evidence supporting both its anti-tumorous and pro-tumorigenic effects [ 9 , 11 ].…”