Effect of non-amidated gastrin peptides on interactions between peroxisome proliferator-activated receptors and the WNT/β-catenin signaling pathway in in vitro models of pancreatic and esophageal cancer

Peroxisome proliferator activated receptor λ coactivator 1α (PGC-1α) is a potent regulator of mitochondrial biogenesis and energy metabolism. In this study, we investigated the therapeutic potential of the secretome released from the adipose-derived stem cells (ASCs) transfected with PGC-1α (PGC-secretome). We first generated PGC-1α-overexpressing ASCs by transfecting ASCs with the plasmids harboring the gene encoding PGC-1α. Secretory materials released from PGC-1α-overexpressing ASCs were collected and their therapeutic potential was determined using in vitro (thioacetamide (TAA)-treated AML12 cells) and in vivo (70% partial hepatectomized mice) models of liver injury. In the TAA-treated AML12 cells, the PGC-secretome significantly increased cell viability, promoted expression of proliferation-related markers, such as PCNA and p-STAT, and significantly reduced the levels of reactive oxygen species (ROS). In the mice, PGC-secretome injections significantly increased liver tissue expression of proliferation-related markers more than normal secretome injections did (p < 0.05). We demonstrated that the PGC-secretome does not only have higher antioxidant and anti-inflammatory properties, but also has the potential of significantly enhancing liver regeneration in both in vivo and in vitro models of liver injury. Thus, reinforcing the mitochondrial antioxidant potential by transfecting ASCs with PGC-1α could be one of the effective strategies to enhance the therapeutic potential of ASCs.

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SASS6 promotes proliferation of esophageal squamous carcinoma cells by inhibiting the p53 signaling pathway

Carcinogenesis ◽

10.1093/carcin/bgaa067 ◽

2020 ◽

Author(s):

Yuanji Xu ◽

Kunshou Zhu ◽

Junqiang Chen ◽

Liyan Lin ◽

Zhengrong Huang ◽

...

Keyword(s):

Esophageal Cancer ◽

Protein Expression ◽

Signaling Pathway ◽

Squamous Carcinoma ◽

Tumor Formation ◽

Squamous Carcinoma Cells ◽

P53 Signaling ◽

P53 Signaling Pathway

Abstract SASS6 encodes for the Homo sapiens SAS-6 centriolar assembly protein and is important for proper centrosome formation. Although centrosomes are amplified in a wide variety of tumor types, abnormally high SASS6 expression had previously only been identified in colon cancer. Moreover, the role of SASS6 in esophageal squamous cell carcinoma (ESCC) pathogenesis has not yet been elucidated. The aim of this study was to investigate the role and mechanisms of SASS6 in ESCC. In this study, we found that the mRNA and protein levels of SASS6 were increased in human ESCC samples. In addition, SASS6 protein expression was associated with the esophageal cancer stage and negatively affected survival of patients with ESCC. Furthermore, silencing of SASS6 inhibited cell growth and promoted apoptosis of ESCC cells in vitro and inhibited xenograft tumor formation in vivo. A genetic cluster and pathway analysis showed that SASS6 regulated the p53 signaling pathway. Western blot demonstrated that CCND2, GADD45A and EIF4EBP1 protein expression decreased and that TP53 protein expression increased after the knockdown of SASS6 in ESCC cells. Therefore, SASS6 promoted the proliferation of esophageal cancer by inhibiting the p53 signaling pathway. SASS6 has potential as a novel tumor marker and a therapeutic target for ESCC.

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PPARδActivity in Cardiovascular Diseases: A Potential Pharmacological Target

PPAR Research ◽

10.1155/2009/745821 ◽

2009 ◽

Vol 2009 ◽

pp. 1-9 ◽

Cited By ~ 4

Author(s):

Angela Tesse ◽

Ramaroson Andriantsitohaina ◽

Thierry Ragot

Keyword(s):

Metabolic Diseases ◽

Peroxisome Proliferator ◽

In Vivo Models ◽

Pharmacological Target ◽

Cardiovascular Cells ◽

Peroxisome Proliferator Activated Receptors

Activation of peroxisome proliferator-activated receptors (PPARs), and particularly of PPARαand PPARγ, using selective agonists, is currently used in the treatment of metabolic diseases such as hypertriglyceridemia and type 2 diabetes mellitus. PPARαand PPARγanti-inflammatory, antiproliferative and antiangiogenic properties in cardiovascular cells were extensively clarified in a variety of in vitro and in vivo models. In contrast, the role of PPARδin cardiovascular system is poorly understood. Prostacyclin, the predominant prostanoid released by vascular cells, is a putative endogenous agonist for PPARδ, but only recently PPARδselective synthetic agonists were found, improving studies about the physiological and pathophysiological roles of PPARδactivation. Recent reports suggest that the PPARδactivation may play a pivotal role to regulate inflammation, apoptosis, and cell proliferation, suggesting that this transcriptional factor could become an interesting pharmacological target to regulate cardiovascular cell apoptosis, proliferation, inflammation, and metabolism.

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Improved Insulin Resistance and Lipid Metabolism by Cinnamon Extract through Activation of Peroxisome Proliferator-Activated Receptors

PPAR Research ◽

10.1155/2008/581348 ◽

2008 ◽

Vol 2008 ◽

pp. 1-9 ◽

Cited By ~ 83

Author(s):

Xiaoyan Sheng ◽

Yuebo Zhang ◽

Zhenwei Gong ◽

Cheng Huang ◽

Ying Qin Zang

Keyword(s):

Insulin Resistance ◽

Target Genes ◽

Water Extract ◽

Food Preparation ◽

Peroxisome Proliferator ◽

Cinnamon Extract ◽

Diet Induced Obesity ◽

Peroxisome Proliferator Activated Receptors ◽

High Caloric Diet

Peroxisome proliferator-activated receptors (PPARs) are transcriptional factors involved in the regulation of insulin resistance and adipogenesis. Cinnamon, a widely used spice in food preparation and traditional antidiabetic remedy, is found to activate PPARγandα, resulting in improved insulin resistance, reduced fasted glucose, FFA, LDL-c, and AST levels in high-caloric diet-induced obesity (DIO) anddb/dbmice in its water extract form. In vitro studies demonstrate that cinnamon increases the expression of peroxisome proliferator-activated receptorsγandα(PPARγ/α) and their target genes such as LPL, CD36, GLUT4, and ACO in 3T3-L1 adipocyte. The transactivities of both full length and ligand-binding domain (LBD) of PPARγand PPARαare activated by cinnamon as evidenced by reporter gene assays. These data suggest that cinnamon in its water extract form can act as a dual activator of PPARγandα, and may be an alternative to PPARγactivator in managing obesity-related diabetes and hyperlipidemia.

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Oxidized fatty acids from Clematis species activate peroxisome proliferator activated receptors (PPARs) in vitro

Planta Medica ◽

10.1055/s-0034-1394719 ◽

2014 ◽

Vol 80 (16) ◽

Author(s):

EM Pferschy-Wenzig ◽

B Lugger ◽

AG Atanasov ◽

C Malainer ◽

EH Heiss ◽

...

Keyword(s):

Fatty Acids ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptors ◽

Oxidized Fatty Acids

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Peroxisome Proliferator-Activated Receptors (PPARs) as Potential Inducers of Antineoplastic Effects in CNS Tumors

PPAR Research ◽

10.1155/2008/204514 ◽

2008 ◽

Vol 2008 ◽

pp. 1-9 ◽

Cited By ~ 4

Author(s):

Lars Tatenhorst ◽

Eric Hahnen ◽

Michael T. Heneka

Keyword(s):

Central Nervous System ◽

Hormone Receptors ◽

Tumor Therapy ◽

Peroxisome Proliferator ◽

Ppar Agonists ◽

The Central Nervous System ◽

Peroxisome Proliferator Activated Receptors ◽

Underlying Mechanisms

The peroxisome proliferator-activated receptors (PPARs) are ligand-inducible transcription factors which belong to the superfamily of nuclear hormone receptors. In recent years it turned out that natural as well as synthetic PPAR agonists exhibit profound antineoplastic as well as redifferentiation effects in tumors of the central nervous system (CNS). The molecular understanding of the underlying mechanisms is still emerging, with partially controverse findings reported by a number of studies dealing with the influence of PPARs on treatment of tumor cells in vitro. Remarkably, studies examining the effects of these drugs in vivo are just beginning to emerge. However, the agonists of PPARs, in particular the thiazolidinediones, seem to be promising candidates for new approaches in human CNS tumor therapy.

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Zinc is essential for the transcription function of the PGC-1α/Nrf2 signaling pathway in human primary endometrial stromal cells

AJP Cell Physiology ◽

10.1152/ajpcell.00152.2019 ◽

2020 ◽

Vol 318 (3) ◽

pp. C640-C648 ◽

Cited By ~ 2

Author(s):

Xiaodan Lu ◽

Qiang Zhang ◽

Li Xu ◽

Xiuying Lin ◽

Jianhua Fu ◽

...

Keyword(s):

Oxidative Stress ◽

Signaling Pathway ◽

Stromal Cells ◽

Receptor Interaction ◽

Peroxisome Proliferator ◽

Related Factor ◽

Stem Cell Markers ◽

Endometrial Stromal Cells ◽

Nrf2 Signaling Pathway

Zinc (Zn) has antioxidant effect in different types of organs and is closely associated with human health. Endometrial receptivity is one of the most important factors in the embryo implantation and development. However, the regulatory mechanism of Zn in endometrium tissue is still unclear. In the study, we found that plasma Zn level is significantly associated with female infertility, which severely affects female reproductive health. Primary endometrial stromal cells were isolated from female endometrium and cultured in the laboratory. Zn chelator TPEN treatment reduced the expression of stem cell markers CD73, CD90, and CD105 and generated reactive oxygen species in endometrial stromal cells. However, pretreatment of Zn (zinc sulfate) is able to prevent TPEN-induced oxidative stress in vitro. By transcriptional profiling and gene ontology analysis, we found that Zn increased the cellular pluripotency signaling and extracellular matrix-receptor interaction, but reduced autophagy, endocytosis, and the nitrogen metabolism pathway. We further discovered the antioxidant function of Zn through the peroxisome proliferator-activated receptor gamma coactivator 1α/nuclear factor erythroid-2-related factor signaling pathway in endometrial stromal cells. Zn supplementation may open up an effective therapeutic approach for patients with oxidative stress-related endometrial diseases.

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