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.
Highlights
Cancer, among all health issues, is a leading concern worldwide
For future reference of further studies on Peroxisome Proliferator-Activated Receptors (PPARs)-g’s cancer treating potential, this review focuses on the recent findings on the functions of PPAR-g, current explorations and discoveries, as well as potential applications of PPAR-g modulators in cancer field
Two separate studies by Ni et al both reported that Efatutazone facilities the treatment of epidermal growth factor receptor (EGFR)-TKIresistant lung adenocarcinoma, by promoting the protein expression of PPAR-g and phosphatase and tensin homolog (PTEN), causing the inactivation of the Akt pathway without affecting the transcriptional levels, which exerts a synergistic effect with LXRa, a member of another class of nuclear hormonal receptor reported being potential targets for the prevention and treatment of multiple cancers, agonist T0901317 [111, 112]
Summary
Among all health issues, is a leading concern worldwide. According to the American Cancer Society, by 2021, it is the second most common cause of death in the US, exceeded only by heart disease. PPAR-g, with two isoforms of PPARg1 and PPARg2, is most highly expressed in adipose tissues, regulating glucose and lipid homeostasis, insulin sensitivity, adipogenesis, inflammation, immune response, and tumorigenesis. Of those said isoforms, PPARg1 is dominant and more universally expressed in various tissues upon biological activation, while PPARg2 is primarily restricted to adipose tissue physiologically, but can be induced in other tissues by high-fat diet (HFD), derived from four different mRNA species (PPARG1, PPARG2, PPARG3 and PPARG4) [10, 11]. Cancers are characterized by aberrated gene mutations, abnormal cell metabolism, low differentiation rate and exceptionally high growth rate [12,13,14]. For future reference of further studies on PPAR-g’s cancer treating potential, this review focuses on the recent findings on the functions of PPAR-g, current explorations and discoveries, as well as potential applications of PPAR-g modulators in cancer field
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