Journal of Cancer Prevention最新文献

House dust mite (HDM) is one of the significant causes for airway inflammation such as asthma. It induces oxidative stress and an inflammatory response in the lungs through the release of chemokines such as interleukin-8 (IL-8). Reactive oxygen species (ROS) activate inflammatory signaling mediators such as mitogen-activated protein kinases (MAPKs) and redox-sensitive transcription factors including NF-κB and AP-1. Ascorbic acid shows an antioxidant and anti-inflammatory activities in various cells. It ameliorated the symptoms of HDM-induced rhinitis. The present study was aimed to investigate whether HDM could induce IL-8 expression through activation of MAPKs, NF-κB, and AP-1 and whether ascorbic acid could inhibit HDM-stimulated IL-8 expression by reducing ROS and suppressing activation of MAPKs, NF-κB, and AP-1 in respiratory epithelial H292 cells. H292 cells were treated with HDM (5 μg/mL) in the absence or presence of ascorbic acid (100 or 200 μM). HDM treatment increased ROS levels, and activated MAPKs, NF-κB, and AP-1 and thus, induced IL-8 expression in H292 cells. Ascorbic acid reduced ROS levels and inhibited activation of MAPKs, NF-κB and AP-1 and L-8 expression in H292 cells. In conclusion, consumption of ascorbic acid-rich foods may be beneficial for prevention of HDM-mediated respiratory inflammation by suppressing oxidative stress-mediated MAPK signaling pathways and activation of NF-kB and AP-1.

The Division of Cancer Prevention of the National Cancer Institute (NCI) and the Office of Disease Prevention of the National Institutes of Health co-sponsored the Translational Advances in Cancer Prevention Agent Development Meeting on August 27 to 28, 2020. The goals of this meeting were to foster the exchange of ideas and stimulate new collaborative interactions among leading cancer prevention researchers from basic and clinical research; highlight new and emerging trends in immunoprevention and chemoprevention as well as new information from clinical trials; and provide information to the extramural research community on the significant resources available from the NCI to promote prevention agent development and rapid translation to clinical trials. The meeting included two plenary talks and five sessions covering the range from pre-clinical studies with chemo/immunopreventive agents to ongoing cancer prevention clinical trials. In addition, two NCI informational sessions describing contract resources for the preclinical agent development and cooperative grants for the Cancer Prevention Clinical Trials Network were also presented.

Patients with cancer are prone to several debilitating side effects including fatigue, insomnia, depression and cognitive disturbances. Beetroot (Beta vulgaris L.) as a health promoting functional food may be potentially beneficial in cancer. As a source of polyphenols, flavonoids, dietary nitrates and other useful nutrients, beetroot supplementation may provide a holistic means to prevent cancer and manage undesired effects associated with chemotherapy. The main aim of this narrative review is to discuss beetroot's nutrient composition, current studies on its potential utility in chemoprevention and cancer-related fatigue or treatment-related side effects such as cardiotoxicity. This review aims to provide the current status of knowledge and to identify the related research gaps in this area. The flavonoids and polyphenolic components present in abundance in beetroot support its significant antioxidant and anti-inflammatory capacities. Most in vitro and in vivo studies have shown promising results; however, the molecular mechanisms underlying chemopreventive and chemoprotective effects of beetroot have not been completely elucidated. Although recent clinical trials have shown that beetroot supplementation improves human performance, translational studies on beetroot and its functional benefits in managing fatigue or other symptoms in patients with cancer are still lacking.

Free fatty acid receptor 2 (FFAR2) has been reported as a tumor suppressor in colon cancer development. The current study investigated the effects of FFAR2 signaling on energy metabolism and gut microbiota profiling in a colorectal cancer mouse model (Apc ^Min/+ ). Ffar2 deficiency promoted colonic polyp development and enhanced fatty acid oxidation and bile acid metabolism. Gut microbiome sequencing analysis showed distinct clustering among wild-type, Apc ^Min/+ , and Apc ^Min/+ -Ffar2 ^-/- mice. The relative abundance of Flavobacteriaceae and Verrucomicrobiaceae was significantly increased in the Apc ^Min/+ -Ffar2 ^-/- mice compared to the Apc ^Min/+ mice. In addition, knocking-down FFAR2 in the human colon cancer cell lines (SW480 and HT29) resulted in increased expression of several key enzymes in fatty acid oxidation, such as carnitine palmitoyltransferase 2, acyl-CoA dehydrogenase, long-chain acyl-CoA dehydrogenase, C-2 to C-3 short chain, and hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase, alpha subunit. Collectively, these results demonstrated that Ffar2 deficiency significantly altered profiles of fatty acid metabolites and gut microbiome, which might promote colorectal cancer development.

Heregulin-β1, a ligand of ErbB-2 and ErbB-3/4 receptors, has been reported to potentiate oncogenicity and metastatic potential of breast cancer cells. In the present work, treatment of human mammary cancer (MCF-7) cells with heregulin-β1 resulted in enhanced cell migration and expression of manganese superoxide dismutase (MnSOD) and its mRNA transcript. Silencing of MnSOD abrogated clonogenicity and migrative ability of MCF-7 cells. Heregulin-β1 treatment also increased nuclear translocation, antioxidant response element binding and transcriptional activity of NF-E2-related factor 2 (Nrf2). A dominant-negative mutant of Nrf2 abrogated heregulin-β1-induced MnSOD expression. Treatment with heregulin-β1 caused activation of protein kinase B (Akt) and extracellular signal-regulated protein kinase (ERK). The pharmacological inhibitors of phosphatidylinositol 3-kinase and mitogen-activated protein kinase kinase 1/2, which are upstream of Akt and ERK, respectively, attenuated heregulin-β1-induced MnSOD expression and nuclear localization of Nrf2. In conclusion, heregulin-1 induces upregulation of MnSOD and activation of Nrf2 via the Akt and ERK signaling in MCF-7 cells, which may confer metastatic potential and invasiveness of these cells.

Helicobacter pylori is recognized as a risk factor for gastric carcinogenesis. The chronic exposure of gastric epithelium to H. pylori induces a prolonged inflammatory state that may progress to gastric cancer. Astaxanthin, a pinkish antioxidant carotenoid, abundant in marine organisms, is known for its protective effect against inflammation and multiple types of cancer. The purpose of this study was to examine the effect of astaxanthin on H. pylori-induced oxidative injury, inflammation, and oncogene expression in gastric mucosal tissues of the infected mice. Mice were inoculated using oral gavage with H. pylori suspension (10⁸ colony forming unit of H. pylori/0.1 mL) for three days, after which they were fed astaxanthin-supplemented diet (5 mg/kg body weight/day for seven weeks). The effects of astaxanthin on H. pylori-induced increase in lipid peroxide (LPO) production, myeloperoxidase (MPO) activity, expression of the inflammatory cytokine IFN-_γ and oncogenes (c-myc and cyclin D1), and the accompanying histologic changes in gastric mucosal tissues were evaluated. H. pylori infection increased the level of LPO, MPO activity, and the expression of IFN-_γ, c-myc, and cyclin D1 in gastric mucosal tissues of mice. H. pylori infection induced neutrophil infiltration and hyperplasia of gastric mucosa. Astaxanthin supplementation attenuated these effects. In conclusion, consumption of astaxanthin-rich foods may prevent H. pylori-associated oxidative damage and inflammatory and oncogenic responses in gastric mucosal tissues.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and is one of the leading causes of cancer-related deaths worldwide. Imatinib and GNF-5 are breakpoint cluster region-Abelson murine leukemia tyrosine kinase inhibitors which have been approved for the treatment of chronic myeloid leukemia and various solid tumors. However, the effect and underlying mechanisms of imatinib and GNF-5 in HCC remain poorly defined. In this study, we investigated the anticancer activity and underlying mechanisms of imatinib and GNF-5 in HepG2 human hepatocarcinoma cells. Cell proliferation and anchorage-independent colony formation assays were done to evaluate the effects of imatinib and GNF-5 on the growth of HepG2 cells. The cell cycle was assessed by flow cytometry and verified by immunoblot analysis. Gene overexpression and knockdown assays were conducted to evaluate the function of S-phase kinase-associated protein 2 (Skp2). Imatinib and GNF-5 significantly inhibited the growth of HepG2 cells. Imatinib and GNF-5 induced G0/G1 phase cell cycle arrest by downregulating Skp2 and upregulating p27 and p21. Overexpression of Skp2 reduced the effect of imatinib and GNF-5 on HepG2 cells. Knockdown of Skp2 suppressed the proliferation and induced G0/G1 phase arrest. Furthermore, knockdown of Skp2 enhanced the effect of imatinib and GNF-5 on growth of HepG2 cells. In conclusion, imatinib and GNF-5 effectively suppress HepG2 cell growth by inhibiting Skp2 expression. Skp2 promotes the cell proliferation and reverse G0/G1 phase cell cycle arrest and it represents a potential therapeutic target for HCC treatment.

Aberrant activation of Ras has been implicated in aggressiveness of breast cancer. Among Ras isoforms (H-, K-, and N-), H-Ras has been known to be primarily responsible for invasion and metastasis of breast cancer cells. Phosphorylation of serine (Ser) or threonine (Thr) is a key regulatory mechanism responsible for controlling activities and functions of various proteins involved in intracellular signal transduction. Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1, Pin1 changes the conformation of a subset of proteins phosphorylated on Ser/Thr that precedes proline (Pro). In this study we have found that Pin1 is highly overexpressed in human breast tumor tissues and H-Ras transformed human mammary epithelial (H-Ras MCF10A) and MDA-MB-231 breast cancer cells. Notably, Pin1 directly bound to the activated form of H-Ras harbouring a Ser/Thr-Pro motif. Pharmacologic inhibition of Pin1 reduced clonogenicity of MDA-MB-231 human breast cancer cells. Paclitaxel accelerates apoptosis in Pin1 silenced H-Ras MCF10A cells. MDR genes (MDR1 and MRP4) were significantly downregulated in MDA-MB-231 cells stably silenced for Pin1. We speculate that Pin1 interacts with GTP-H-Ras, thereby upregulating the expression of drug resistance genes, which confers survival advantage and aggressiveness of breast cancer cells under chemotherapy.

A transcription factor Sry-related high mobility group box (Sox) 17 is involved in developmental processes including spermatogenesis, cardiovascular system, endoderm formation, and so on. In this article, we firstly review the studies on the relation between the Sox17 expression and tumor malignancy. Although Sox17 positively promotes various tissue development, most of the cancers associated with Sox17 show decreased expression levels of Sox17, and an inverse correlation between Sox17 expression and malignancy is revealed. We briefly discuss the mechanism of such Sox17 down-regulation by focusing on DNA methylation of CpG sites located in the Sox17 gene promoter. Next, we overview the function of Sox17 in the fetal hematopoiesis, particularly in the dorsal aorta in midgestation mouse embryos. The Sox17 expression in hematopoietic stem cell (HSC)-containing intra-aortic hematopoietic cell cluster (IAHCs) is important for the cluster formation with the hematopoietic ability. The sustained expression of Sox17 in adult bone marrow HSCs and the cells in IAHCs of the dorsal aorta indicate abnormalities that are low lymphocyte chimerism and the aberrant proliferation of common myeloid progenitors in transplantation experiments. We then summarize the perspectives of Sox17 research in cancer control.

Natural compounds from diverse sources, including botanicals and commonly consumed foods and beverages, exert beneficial health effects via mechanisms that impact the epigenome and gene expression during disease pathogenesis. By targeting the so-called epigenetic 'readers', 'writers', and 'erasers', dietary phytochemicals can reverse abnormal epigenome signatures in cancer cells and preneoplastic stages. Thus, such agents provide avenues for cancer interception via prevention or treatment/therapeutic strategies. To date, much of the focus on dietary agents has been directed towards writers (e.g., histone acetyltransferases) and erasers (e.g., histone deacetylases), with less attention given to epigenetic readers (e.g., BRD proteins). The drug JQ1 was developed as a prototype epigenetic reader inhibitor, selectively targeting members of the bromodomain and extraterminal domain (BET) family, such as BRD4. Clinical trials with JQ1 as a single agent, or in combination with standard of care therapy, revealed antitumor efficacy but not without toxicity or resistance. In pursuit of second-generation epigenetic reader inhibitors, attention has shifted to natural sources, including dietary agents that might be repurposed as 'JQ1-like' bioactives. This review summarizes the current status of nascent research activity focused on natural compounds as inhibitors of BET and other epigenetic 'reader' proteins, with a perspective on future directions and opportunities.