PPAR-α Modulators as Current and Potential Cancer Treatments

Tan, Yan; Wang, Mina; Yang, Ke; Chi, Tiange; Liao, Ziqi; Wei, Peng

doi:10.3389/fonc.2021.599995

Cited by 80 publications

(57 citation statements)

References 133 publications

(130 reference statements)

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“…PPARs belong to the nuclear hormone receptors that are activated by fatty acids and their derivatives. PPARs play a critical role in modulating the gene expressions which involves in the glucose and lipid metabolism, adipogenesis and inflammation [ 37 , 38 ]. PPAR signaling pathway was predicted to be lower in the TPEE treated group than in the NC group.…”

Section: Discussionmentioning

confidence: 99%

Trifolium pratense ethanolic extract alters the gut microbiota composition and regulates serum lipid profile in the ovariectomized rats

Quah

Park

Lee

et al. 2022

BMC Complement Med Ther

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Background Trifolium pratense (red clover) ethanolic extract (TPEE) has been used as a popular over-the-counter remedy for the management of menopausal symptoms. Prolonged consumption of herbal extract has been shown to regulate the composition of gut microbiota. This study was designed to elucidate the influence of TPEE on the gut microbiota composition in the ovariectomized (OVX) rats. Methods OVX rats were treated with TPEE at 125, 250, 500 mg/kg/day, or controls (pomegranate extract, 500 mg/kg/day; estradiol, 25 μg/kg/day) for 12 weeks. Gut microbiota analysis was conducted by extracting the microbial DNA from fecal samples and microbiome taxonomic profiling was carried out by using next-generation sequencing. The levels of serum biomarkers were analyzed using enzyme-linked immunosorbent assay (ELISA) kit. The prediction of functional biomarker of microbiota was performed using PICRUSt to investigate the potential pathways associated with gut health and serum lipid profile regulation. To study the correlation between gut microbiota composition and serum lipid levels, Spearman’s correlation coefficients were defined and analyzed. Additionally, gas chromatography–mass spectrometry analysis was conducted to uncover additional physiologically active ingredients. Results TPEE-treated OVX rats showed significant reduction in serum triglycerides (TG), total cholesterols (TCHOL), and LDL/VLDL levels but increase in HDL level. The alteration in the pathways involve in metabolism was the most common among the other KEGG categories. Particularly, TPEE also significantly reduced the relative abundance of sequences read associated with inflammatory bowel disease (IBD) and the peroxisome proliferator-activated receptor (PPAR) signalling pathway. TPEE intervention was seen to reduce the Firmicutes to Bacteroidetes (F/B) ratio in the OVX rats, denoting a reduction in microbial dysbiosis in the OVX rats. Correlation analysis at the phylum level revealed that Bacteriodetes and Proteobacteria were strongly correlated with serum TG, TCHOL and HDL levels. At the species level, Bifidobacterium pseudolongum group was seen to positively correlate with serum HDL level and negatively correlated with serum AST, ALT, LDL/VLDL, TCHOL, and TG levels. Conclusions TPEE treatment showed therapeutic benefits by improving the intestinal microbiota composition which strongly correlated with the serum lipid and cholesterol levels in the OVX rats.

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Section: Discussionmentioning

confidence: 99%

Trifolium pratense ethanolic extract alters the gut microbiota composition and regulates serum lipid profile in the ovariectomized rats

Quah

Park

Lee

et al. 2022

BMC Complement Med Ther

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“…Peroxisome Proliferator-Activated Receptors (PPARs) are ligand-inducible transcription factors, belonging to the nuclear receptor superfamily ( 6 , 7 ). Upon ligand-binding, PPARs translocate to the nucleus, after binding to peroxisome proliferator response elements (PPREs) on DNA and heterodimerizing with retinoid X receptor, they modulate the transcription of target genes.…”

Section: Introductionmentioning

confidence: 99%

PPAR-γ Modulators as Current and Potential Cancer Treatments

Chi

Wang

et al. 2021

Front. Oncol.

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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.

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“…The peroxisome proliferator activated receptors (PPARs) are ligand‐activated transcription factors of nuclear receptor superfamily that comprises the subtypes PPARα, PPARγ, and PPARβ/δ (Tyagi et al, 2011; Wagner & Wagner, 2020b). Activation of PPAR is related to the modulation of multiple physiological processes, including cell metabolism, cancer, cardiovascular functioning, and so forth (Jumpertz et al, 2011; Tan et al, 2021; Wagner & Wagner, 2020b). Among the endogenous ligands that activate PPARα are the lipids oleoylethanolamide (OEA) and palmitoylethanolamide (PEA; Carta et al, 2015; Chen et al, 2015; Grygiel‐Górniak, 2014; Tutunchi et al, 2019; Tutunchi, Naeini, Saghafi‐Asl, Farrin, et al, 2020; Tutunchi, Ostadrahimi, Saghafi‐Asl, Hosseinzadeh‐Attar, et al, 2020; Tutunchi, Saghafi‐Asl, & Ostadrahimi, 2020).…”

Section: Discussionmentioning

confidence: 99%

In vivo brain levels of acetylcholine and 5‐hydroxytryptamine after oleoylethanolamide or palmitoylethanolamide administrations are mediated by PPARα engagement

Murillo-Rodrı́guez

Arankowsky‐Sandoval

Budde

et al. 2021

Eur J of Neuroscience

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The peroxisome proliferator‐activated receptor alpha (PPARα) is a nuclear receptor that has been linked to the modulation of several physiological functions, including the sleep–wake cycle. The PPARα recognizes as endogenous ligands the lipids oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), which in turn, if systemically injected, they exert wake‐promoting effects. Moreover, the activation of PPARα by the administration of OEA or PEA increases the extracellular contents of neurotransmitters linked to the control of wakefulness; however, the role of PPARα activated by OEA or PEA on additional biochemicals related to waking regulation, such as acetylcholine (ACh) and 5‐hydroxytryptamine (5‐HT), has not been fully studied. Here, we have investigated the effects of treatments of OEA or PEA on the contents of ACh and 5‐HT by using in vivo microdialysis techniques coupled to HPLC means. For this purpose, OEA or PEA were systemically injected (5, 10 or 30 mg/kg; i.p.), and the levels of ACh and 5‐HT were collected from the basal forebrain, a wake‐related brain area. These pharmacological treatments significantly increased the contents of ACh and 5‐HT as determined by HPLC procedures. Interestingly, PPARα antagonist MK‐886 (30 mg/kg; i.p.) injected before the treatments of OEA or PEA blocked these outcomes. Our data suggest that the activation of PPARα by OEA or PEA produces significant changes on ACh and 5‐HT levels measured from the basal forebrain and support the conclusion that PPARα is a suitable molecular element involved in the regulation of wake‐related neurotransmitters.

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PPAR-α Modulators as Current and Potential Cancer Treatments

Cited by 80 publications

References 133 publications

Trifolium pratense ethanolic extract alters the gut microbiota composition and regulates serum lipid profile in the ovariectomized rats

Trifolium pratense ethanolic extract alters the gut microbiota composition and regulates serum lipid profile in the ovariectomized rats

PPAR-γ Modulators as Current and Potential Cancer Treatments

In vivo brain levels of acetylcholine and 5‐hydroxytryptamine after oleoylethanolamide or palmitoylethanolamide administrations are mediated by PPARα engagement

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