The growth of human cancer cells expressing peroxisome proliferator-activated receptor-gamma (PPAR-gamma) has been reported to be inhibited by PPAR-gamma ligands. In esophageal squamous-cell carcinoma cell lines T.T, T.Tn, and EC-GI-10, we detected expression of PPAR-gamma and investigated the effects of PPAR-gamma ligands on these cell lines in vitro with the use of troglitazone, pioglitazone, and 15d-PGJ2. Marked growth inhibition by the PPAR-gamma ligands was observed in all cases. The growth-inhibitory effect was evidenced by a dose-dependent inhibition of deoxyribonucleic acid synthesis and was associated with altered cell-cycle progression manifesting G1 arrest. Cell-cycle arrest in T.Tn cells induced by troglitazone could be correlated with an increased level of cyclin-dependent kinase inhibitor p27(Kip1), p21(Cip1/Waf1), and p18(Ink4c). Moreover, troglitazone treatment increased the expression of interleukin-1 alpha, a multifunctional cytokine implicated in antitumor immunity. These findings suggest that troglitazone and other PPAR-gamma ligands have adjuvant or neoadjuvant therapeutic potentials in esophageal cancer.
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http://dx.doi.org/10.1067/mlc.2002.125055 | DOI Listing |
Microsc Res Tech
January 2025
Department of Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt.
Arrhythmia is a common and serious global health problem, contributing to cardiovascular morbidity and mortality. The cardiac muscle is susceptible to ischemia-reperfusion (I/R) injury, which can lead to fatal arrhythmias during open-heart surgery. We investigated the potential prophylactic effect of angiotensin 1-7 (Ang 1-7) using an in vivo rat model of I/R injury and examined the underlying mechanisms.
View Article and Find Full Text PDFInt Immunopharmacol
February 2025
Department of Neurosurgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006 Jiangxi, China; Jiangxi Key Laboratory of Neurological Tumors and Cerebrovascular Diseases, Nanchang 330006 Jiangxi, China; Jiangxi Health Commission Key Laboratory of Neurological Medicine, Nanchang 330006 Jiangxi, China; Institute of Neuroscience, Nanchang University, Nanchang 330006 Jiangxi, China. Electronic address:
The pathological mechanisms of Parkinson's disease (PD) is complex, and no definitive cure currently exists. This study identified Rutaecarpine (Rut), an alkaloid extracted from natural plants, as a potential therapeutic agent for PD. To elucidate its mechanisms of action and specific effects in PD, network pharmacology, molecular docking, and experimental validation methods were employed.
View Article and Find Full Text PDFBiol Direct
December 2024
School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, India.
Peroxisome proliferator-activated receptor-γ (PPARγ) is a critical regulator of adipogenesis and bone metabolism, playing complex roles in osteoporosis. This study investigates the effects of taurine and homocysteine on PPARγ, focusing on their roles in osteoclastogenesis and bone health. In-silico analyses, including molecular docking and molecular dynamic simulations, revealed that both taurine and homocysteine bind competitively to the PPARγ ligand-binding domain, exhibiting distinctive antagonistic modes, including destabilization of PPARγ's key helices H3, H4/5, H11, and H12.
View Article and Find Full Text PDFBioorg Chem
January 2025
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea; Future Medicine Co., Ltd, 54 Changup-ro, Sujeong-gu, Seongnam, Gyeonggi-do 13449, Republic of Korea. Electronic address:
This study explores the synthesis and evaluation of truncated 1'-homologated 4'-selenonucleosides as dual modulators of PPARγ and PPARδ. Starting with d-lyxose, a 4'-selenosugar was synthesized and condensed with a nucleobase via an S2 reaction, followed by modifications at the C2- and N-positions, yielding compounds 3a-l. Structure-activity trend analysis identified compound 3h, featuring 2-chloro and N-3-iodobenzylamine substituents, as a potent PPARγ partial agonist and PPARδ antagonist (PPARγ K = 2.
View Article and Find Full Text PDFJ Cell Mol Med
December 2024
Department of Parasitology and Medical Entomology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
Tetracarpidium conophorum nuts are nutrient-dense Nigerian snacks associated with weight regulation. This study explores the nuts' impact on adipose tissue gene expression associated with low-grade inflammation. Ethanol whole extract (EWE), ethyl-acetate fraction (EAF) and the resulting residue (RES) were orally administered once daily to MSG-induced obese rats for 6 weeks (n = 6).
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