Background A. oxyphylla extract is known to possess a wide range of pharmacological activites. However, the molecular mechanism of A. oxyphylla and its bioactive compound nootkatone in colorectal cancer is unknown. Methods Our study aims to examine the role of A. oxyphylla and its bioactive compound nootkatone, in tumor suppression using several in vitro assays. Results Both A. oxyphylla extract and nootkatone exhibited antiproliferative activity in colorectal cancer cells. A. oxyphylla displayed antioxidant activity in colorectal cancer cells, likely mediated via induction of HO-1. Furthermore, expression of pro-apoptotic protein NAG-1 and cell proliferative protein cyclin D1 were increased and decreased respectively in the presence of A. oxyphylla. When examined for anticancer activity, nootkatone treatment resulted in the reduction of colony and spheroid formation. Correspondingly, nootkatone also led to increased NAG-1 expression and decreased cyclin D1 expression. The mechanism by which nootkatone suppresses cyclin D1 involves protein level regulation, whereas nootkatone increases NAG-1 expression at the transcriptional level. In addition to having PPARγ binding activity, nootkatone also increases EGR-1 expression which ultimately results in enhanced NAG-1 promoter activity. Conclusion In summary, our findings suggest that nootkatone is an anti-tumorigenic compound harboring antiproliferative and pro-apoptotic activity.
Nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1) plays a role in various diseases. Here, the anti-diabetic effects of NAG-1 were evaluated using a high-fat diet/streptozotocin-induced diabetic mouse model. NAG-1-overexpressing transgenic (NAG-1 Tg) mice exhibited lower body weight, fasting blood glucose levels, and serum insulin levels than wild-type (WT) mice. The homeostatic model assessment of insulin resistance scores of NAG-1 Tg mice were lower than those of WT mice. Hematoxylin and eosin staining revealed a smaller lipid droplet size in the adipose tissues, lower lipid accumulation in the hepatocytes, and larger beta cell area in the pancreas of NAG-1 Tg mice than in those of WT mice. Immunohistochemical analysis revealed downregulated expression of cleaved caspase-3, an apoptosis marker, in the beta cells of NAG-1 Tg mice. Adiponectin and leptin mRNA levels were upregulated and downregulated in NAG-1 Tg mice, respectively. Additionally, the expression of IRS1/PI3K/AKT signaling pathway components, especially Foxo1, which regulates gluconeogenesis in the muscle and white adipose tissue, was downregulated in NAG-1 Tg mice. Furthermore, NAG-1 overexpression promoted the expression of As160 in both muscles and adipocytes, and the mRNA levels of the NLRP3 pathway members were downregulated in NAG-1 Tg mice. Our findings suggest that NAG-1 expression alleviates diabetes in mice.
Although the treatment of thyroid cancer has improved, unnecessary surgeries are performed due to a lack of specific diagnostic and prognostic markers. Therefore, the identification of novel biomarkers should be considered in the diagnosis and treatment of thyroid cancer. In this study, antibody arrays were performed using tumor and adjacent normal tissues of patients with papillary thyroid cancer, and several potential biomarkers were identified. Among the candidate proteins chosen based on the antibody array data, mature NAG-1 exhibited increased expression in tumor tissues compared to adjacent normal tissues. In contrast, pro-NAG-1 expression increased in normal tissues, as assessed by western blot analysis. Furthermore, pro-NAG-1 expression was increased when the thyroid cancer cells were treated with phytochemicals and nonsteroidal anti-inflammatory drugs in a dose-dependent manner. In particular, quercetin highly induced the expression of pro-NAG-1 but not that of mature NAG-1, with enhanced anticancer activity, including apoptosis induction and cell cycle arrest. Examination of the NAG-1 promoter activity showed that p53, C/EBPα, or C/EBPδ played a role in quercetin-induced NAG-1 expression. Overall, our study indicated that NAG-1 may serve as a novel biomarker for thyroid cancer prognosis and may be used as a therapeutic target for thyroid cancers.
Despite intensive research efforts in recent decades, cancer remains a leading cause of death worldwide. The chalcone family is a promising group of phytochemicals for therapeutic use against cancer development. Naturally-occurring chalcones, as well as synthetic chalcone analogues, have shown many beneficial biological properties, including anti-inflammatory, antioxidant, and anti-cancer activities. In this report, trans-chalcone (TChal) was found to increase cell death in breast cancer cells, assessed using high content screening. Subsequently, using antibody array analysis, TChal was found to increase heme oxygenase-1 (HO-1) expression in TChal-treated breast cancer cells. Blocking of HO-1 by siRNA in breast cancer cells diminished the effect of TChal on cell growth inhibition. TChal-fed mice also showed less tumor growth compared to vehicle-fed mice. Overall, we found that TChal increases HO-1 expression in breast cancer cells, thereby enhancing anti-tumorigenesis. Our results suggest that HO-1 expression could be a potential new target of TChal for anti-tumorigenesis in breast cancer.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.