Cancer Preventive Effects Research Articles

The Potential Role of Fisetin, a Flavonoid in Cancer Prevention and Treatment.

Cancer is a main culprit and the second-leading cause of death worldwide. The current mode of treatment strategies including surgery with chemotherapy and radiation therapy may be effective, but cancer is still considered a major cause of death. Plant-derived products or their purified bioactive compounds have confirmed health-promoting effects as well as cancer-preventive effects. Among these products, flavonoids belong to polyphenols, chiefly found in fruits, vegetables and in various seeds/flowers. It has been considered to be an effective antioxidant, anti-inflammatory and to play a vital role in diseases management. Besides these activities, flavonoids have been revealed to possess anticancer potential through the modulation of various cell signaling molecules. In this regard, fisetin, a naturally occurring flavonoid, has a confirmed role in disease management through antioxidant, neuro-protective, anti-diabetic, hepato-protective and reno-protective potential. As well, its cancer-preventive effects have been confirmed via modulating various cell signaling pathways including inflammation, apoptosis, angiogenesis, growth factor, transcription factor and other cell signaling pathways. This review presents an overview of the anti-cancer potential of fisetin in different types of cancer through the modulation of cell signaling pathways based on in vivo and in vitro studies. A synergistic effect with anticancer drugs and strategies to improve the bioavailability are described. More clinical trials need to be performed to explore the anti-cancer potential and mechanism-of-action of fisetin and its optimum therapeutic dose.

Secondary Metabolites in Fungi

Fungi are a biological family that includes multicellular and unicellular eukaryotic organisms in general. They are quite numerous and diverse. It is the second largest group of organisms on Earth after insects. Higher fungi (terrestrial fungi) currently constitute a large and efficiently untapped resource of new pharmacological crops with nutritional values are potentially powerful. Antioxidants prevent cellular damage caused by free radicals in living beings. It has been found that 36% of endophytic mushroom extracts with a high phenolic content show strong antioxidant effects. In one study, they reported that the antioxidant activities of the strains Aspergillus sp., A. niger, A. peyronelii and Chaetomium sp. ranged from 50% to 80% and that this antioxidant activity was due to their high phenolic content. In addition to the antioxidant properties of fungi, it has been shown as a result of research that they show antibacterial activity. Macrofungal β-glucans (β-1,6 glycosidic bonds and mainly β-1,3), which are known to have immunomodulatory and antitumor effects in cancer prevention, can be used in treatment strategies. At the same time, it has been shown in studies that these metabolites obtained from fungi cause fewer side effects when used in treatments, unlike chemical drugs. As a result of phytochemical research, the presence of flavonoids, anthraquinones, steroids, terpenoids, coumarins, phenols and tannins in fungal extracts in general was detected, while alkaloids and saponins were not found. It has been determined that the studies on mushrooms have gained versatile uses since they reveal secondary metabolite components with different biological activities in the structure of these group members.

Mechanism Underlying Metformin Action and Its Potential to Reduce Gastric Cancer Risk.

Diabetes mellitus is associated with a high risk of developing gastric cancer (GC). Metformin, which is conventionally used to treat type 2 diabetes, induces AMP-activated protein kinase signaling and suppresses gluconeogenesis. Recent studies have reported that metformin is associated with beneficial effects in cancer prevention and treatment owing to its anti-tumor effects. This makes metformin a potential medication for GC therapy. However, contradicting reports have emerged regarding the efficacy of metformin in reducing the risk of GC. This review summarizes the impact of metformin on mitigating GC risk by analyzing clinical databases. The mechanism underlying the anti-tumor effect of metformin on GC is also discussed.

The Potential Functions and Mechanisms of Oat on Cancer Prevention: A Review.

Oat is classified as a whole grain and contains high contents of protein, lipids, carbohydrates, vitamins, minerals, and phytochemicals (such as polyphenols, flavonoids, and saponins). In recent years, studies have focused on the effects of oat consumption on reducing the risk of a variety of diseases. Reports have indicated that an oat diet exerts certain biological functions, such as preventing cardiovascular diseases, reducing blood glucose, and promoting intestinal health, along with antiallergy, antioxidation, and cancer preventive effects. At present, cancer is the second leading cause of death worldwide. The natural products of oat are an important breakthrough for developing new strategies of cancer prevention, and their ability to interact with multiple cellular targets helps to combat the complexity of cancer pathogenesis. In addition, the comprehensive study of the cancer prevention activity and potential mechanism of oat nutrients and phytochemicals has become a research hotspot. In this Review, we focused on the potential functions of peptides, dietary fiber, and phytochemicals in oats on cancer prevention and further revealed novel mechanisms and prospects for clinical application. These findings might provide a novel approach to deeply understand the functions and mechanisms for cancer prevention of oat consumption.

Identification of natural product 3, 5-diiodotyrosine as APOBEC3B inhibitor to prevent somatic mutation accumulation and cancer progression

BackgroundThe development of cancer is largely dependent on the accumulation of somatic mutations, indicating the potential to develop cancer chemoprevention agents targeting mutation drivers. However, ideal cancer chemoprevention agents that...

Cancer Prevention Sense Making and Metaphors in Young Women's Invented Stories.

Despite the proven effectiveness of cancer prevention, the literature highlights numerous obstacles to the adoption of screening, even at a young age. In cancer discourse, the metaphor of war is omnipresent and reflects an imperative demand to win the war against disease. From the psychodynamic perspective, the risk of cancer forecasts an emotionally critical experience for which it is important to study mental representations concerning illness and health care. Through the creation of an invented story that offers a framework for imagination, our aim is to understand what the relationship with preventive practices in oncology means for young women and how this relationship is revealed by their metaphors. A total of 58 young women voluntarily participated in the present research, answering a narrative prompt. The stories written by the participants were analyzed using qualitative methodology to identify construct, themes and metaphors. Our findings identify four constructs: the construction of a defense: youth as protection; the attribution of blame about cancer risk; learning from experience as a prevention activator; and from inaccessibility to access to preventive practices: the creation of engagement. The construction of an invented story allows us to promote a process of prefiguration on the bodily, affective and thought planes invested in preventive practice and brings out the use of metaphors to represent cancer risk and self-care. The results allow us to think about the construction of interventions to promote engagement processes in prevention from an early age.

Prospects for personalized Helicobacter pylori eradication therapy. Pro et contra

The article is devoted to debatable aspects of Helicobacter pylori eradication therapy. The eradication cancer-preventive effects are considered. A negative comorbidity between H. pylori infection and such diseases as gastroesophageal reflux disease, inflammatory bowel disease and bronchial asthma has been described. The perspectives of populational, individualized and personalized strategies for H. pylori eradication therapy assessment are given. Recommendations for individualized H. pylori eradication strategy implementation in practical healthcare are proposed.

Risk factors of malignancy

Prevention strategies aim to change environmental and lifestyle risk factors that contribute to the development of cancer. Screening detects abnormalities before they become clinically apparent, allowing intervention either before cancer develops or at an early stage when treatment is most likely to be effective. Despite reliable data on factors that reduce the risk of neoplasms, in routine clinical practice, the effectiveness of cancer prevention is still not high enough. This determines the high importance of the topic of this review, which summarizes the current scientific data on risk factors for the development of oncopathology and ways to influence them. Such risk factors as lifestyle, alcohol and tobacco use, physical activity, nutrition and other environmental factors are considered. A large role is given to infections, which is also considered in this review. The article highlights the intake of vitamins and microelements for the purpose of cancer prevention, as well as the influence of certain drugs taken to treat non-oncological diseases on the development of oncopathology. The purpose of the review is to present an analysis of current literature data on the methods of cancer prevention.

126 (PB116) - Immunomodulatory effects of low piperine fractional Piper nigrum extract on breast cancer prevention

Background: Piper nigrum, black pepper, has various biological effects such as anti-microbial, anti-inflammatory and anti-cancer activities. A crude extract of P. nigrum named low piperine fractional Piper nigrum extract (PFPE) has been reported for anti-tumor and anti-tumor immunity on breast cancer. PFPE also had an ability on cancer prevention. However, the mechanism of action of PFPE on cancer prevention has not been elucidated yet. Here, we evaluated the immunomodulatory role of PFPE on the prevention of breast cancer in mammary tumor rat model. Material and methods: Female Sprague-Dawley rats, 45 days old (virgin) were divided into 6 groups, including normal, control, vehicle (MCT and vitamin E) and PFPE at doses of 50, 100 and 150 mg/kg BW. Rats were injected with 250 mg/kg BW of NMU at 50 and 80 days old and fed with 100 μg/kg BW of estradiol after 7 days of 2nd NMU injection for 10 days. The PFPE was orally administered after 5 days of the 1st NMU injection, 3 times per week for 91 days. The blood from lateral tail vein was collected for cytokine study at 15 and 61 days after PFPE treatment. At the end of the experiment, rats were sacrificed and collected blood by cardiac puncture for investigation of blood parameters, ROS production, cytokines, chemokines and immune cell types. Internal organs were weighed, and tumor tissues were collected for histology study. Results: The cancer preventive effects of PFPE at a dose of 50, 100 and 150 mg/kg BW were 71.43, 71.43 and 100%, respectively. Meanwhile vehicle prevented breast cancer at 28.57%. There were no significant changes in organ/body weight ratio and blood parameters, except for alkaline phosphatase at a dose of 150 mg/kg BW. For the histological study, tumors of the control rats were invasive ductal carcinoma, while the rats treated with PFPE at doses of 50 and 100 mg/kg BW were ductal carcinoma in situ. In addition, PFPE treatment at a dose of 100 and 150 mg/kg BW represented amount of ROS higher than non-treated and vehicle groups. PFPE at doses of 50 and 150 mg/kg BW suppressed cytokines and chemokines compared to control and vehicle groups at 15 days after PFPE treatment. Moreover, PFPE at a dose of 100 mg/kg BW was the most effective dose at 61 and 91 days after treatment. Interestingly, all doses of PFPE stimulated IFN-γ at the endpoint of experiment. PFPE at doses of 100 and 150 mg/kg BW significantly promoted type 1 T helper cells and inhibited type 2 T helper cells and regulatory T cells compared to non-treated and vehicle groups. Conclusions: These results indicate that PFPE at doses of 100 and 150 mg/kg BW had efficacy on immunomodulation in cancer prevention through the regulation of ROS, Th1/Th2/Treg and cytokine/chemokine production. However, PFPE at a dose of 150 mg/kg BW should be carefully used for a long time due to its adverse effect on liver function. No conflict of interest.

Fenretinide combines perturbation of signaling kinases, cell-extracellular matrix interactions and matrix metalloproteinase activation to inhibit invasion in oral squamous cell carcinoma cells.

Basement membrane invasion defines malignant transformation of surface premalignancy. Treatment of oral squamous cell carcinoma (OSCC) cells with the synthetic vitamin A derivative, fenretinide (4HPR), induces numerous cancer-preventive effects including suppression of basement membrane invasion, elimination of anchorage-independent growth, disruption of actin cytoskeletal components and inhibition of the invasion-enabling focal adhesive kinase. The purpose of this study was to elucidate 4HPR’s effects on additional invasion-relevant mechanisms including matrix metalloproteinase (MMP) activation and function, cell–extracellular matrix (ECM) attachments and interaction with a kinase that is essential for the epithelial–myoepithelial transformation i.e. c-Jun NH2-terminal kinase (JNK). Our data revealed that 4HPR binds with high affinity to the ATP-binding site of all three JNK isoforms with concurrent suppression of kinase function. Additional studies showed 4HPR treatment inhibited both OSCC cell–ECM adhesion and MMP activation and function. JNK downregulation and induced expression studies confirmed that the JNK3 isoform conveyed that largest impact on OSCC migration and invasion. Biodegradable polymeric implants formulated to preserve 4HPR’s function and bioavailability were employed to assess 4HPR’s chemopreventive impact on an OSCC tumor induction model. These studies revealed 4HPR local delivery significantly inhibited OSCC tumor size, mitotic indices and expression of the endothelial marker, erythroblast transformation-specific-related gene with concurrent increases in tumor apoptosis (cleaved caspase-3). Collectively, these data show that 4HPR suppresses invasion at multiple sites including ‘outside-in’ signaling, cell–ECM interactions and suppression of MMPs. These functions are also essential for physiologic function. Regulation is therefore essential and reinforces the pharmacologic advantage of local delivery chemopreventive formulations. .

Relationship Between Leukotriene Receptor Antagonists on Cancer Development in Patients With Bronchial Asthma: A Retrospective Analysis.

An association between leukotriene receptor antagonists (LTRA) and cancer has been previously reported, but the relationship between LTRA use and cancer prevention remains controversial. This study aimed to clarify the cancer-preventive effect of LTRA in Japanese patients with bronchial asthma. We obtained information from a large populationbased medical information database to analyze data on patients who were newly diagnosed with bronchial asthma between 2006 and 2015. Eligible participants were patients who were prescribed an LTRA for at least 30 days (LTRA users) and those who were not using LTRA (LTRA non-users) during the objective period. LTRA users and LTRA non-users were matched 1:1 using propensity scores. The 1:1 propensity score matching of LTRA users and LTRA nonusers facilitated the inclusion of 3,744 participants each, in these two subgroups. The results of the Cox proportional hazards model after adjustment for covariates showed no significant difference in the cancer risk between LTRA users and non-users [adjusted hazard ratio (HR)=0.83, 95% confidence interval (CI)=0.59-1.16]. The subgroup analysis showed no significant difference in the cancer risk between the LTRA low-cumulative dose group and LTRA non-users, or between the LTRA medium-cumulative dose group and LTRA non-users. In contrast, the LTRA high-cumulative dose group had a significantly lower risk of developing cancer compared with LTRA non-users (adjusted HR=0.57, 95% CI=0.33-0.98). LTRA use may prevent cancer in patients with bronchial asthma.

Association of Dietary Carrot/Carotene Intakes With Colorectal Cancer Incidence and Mortality in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

Background:The evidence of dietary carrot/carotene intake's effect on the association with colorectal cancer (CRC) risk is conflicted. We sought to examine the association of carrot/carotene intake with CRC incidence and mortality in the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening cohort.MethodsIn all, 101,680 participants were enrolled between November 1993 and July 2001 from the PLCO cohort. We employed the multivariable Cox regression analyses to estimate the hazard ratios and 95% confidence interval. Subgroup analyses and interaction tests were performed to examine the potential effect modifiers. We further applied the generalized additive model to explore the non-linear trend of the exposure to cancer-related outcomes.ResultsA total of 1,100 CRC cases and 443 cancer-related deaths were documented. We noted that the 4th quintile of dietary carrot intakes was associated with a 21% lower risk of CRC incidence, compared with the lowest quintile group (full-adjusted HRquintile4vs.quintile1 = 0.79, 95%CI = 0.65–0.97, p for trend = 0.05), while the adjusted-HR was 0.95 (95%CI = 0.89–1.02) with per SD increment of carrot intakes, and no statistically significant associations were detected between dietary α-, and β-carotene intake and CRC incidence. There were no statistically significant associations observed between carrot/carotene intakes and CRC mortality. Furthermore, there were no non-linear dose-response relationships between dietary carrot, α-, and β-carotene intake and CRC incidence and mortality (all pnonlinearity > 0.05). Of note, smoking status as a modifier on the association of dietary carrot intakes with CRC incidence but not mortality was observed.ConclusionsIn summary, this large U.S. prospective cohort study indicated that a moderate consumption of carrots was associated with a lower CRC incidence, which suggested that a certain dose-range of carrots consumed might contribute to a potential cancer-prevention effect, not the more the better.

Lutein Induces Apoptosis of Gastric Cancer Cells by Producing Reactive Oxygen Species via NADPH Oxidase Activation

ObjectivesApoptosis is well known for its relationship with cancer. Disruption of apoptosis leads to tumor progression, and many cytotoxic anticancer agents induce apoptosis. As a class of phytochemicals, carotenoids are fat-soluble pigments that are abundant in fruits and vegetables and have health-promoting properties, including cancer prevention effects. The anticancer effects of carotenoids are related to their pro-oxidant activities. Lutein is a type of vitamin called a carotenoid. A recent study showed that lutein inhibits the growth of breast cancer cells. The present study was purposed to determine whether lutein induces apoptosis of gastric cancer cells through reactive oxygen species (ROS)-mediated mechanism. MethodsHuman gastric cancer cell line, AGS was treated with lutein. Cell viability was determined by counting the number of viable cells. The protein levels of Bax, Bcl-2, active caspase-3 were examined by western blot analysis. DNA fragmentation was determined by Cell Death Detection ELISA. DCF-DA fluorescence technique was used to quantify the intracellular ROS level. NADPH oxidase activity was measured by lucigenin assay. Colony formation assay was performed and colonies were counted. ResultsLutein decreased cell viability in a dose-dependent manner. Colony formation was also inhibited by lutein. Lutein increased Bax/Bcl-2 ratio, caspase-3 activity, and DNA fragmentation. The intracellular ROS level and NADPH oxidase activity were increased. The decrease in cell viability by lutein was reversed by ML171 (NADPH oxidase 1 specific inhibitor) and N-acetyl cysteine (NAC; antioxidant). ConclusionsLutein induce apoptosis of gastric cancer cells by increasing NADPH oxidase-mediated ROS production. Funding SourcesNo funding sources.

Obesity and Pancreatic Cancer: Recent Progress in Epidemiology, Mechanisms and Bariatric Surgery.

More than 30% of people in the United States (US) are classified as obese, and over 50% are considered significantly overweight. Importantly, obesity is a risk factor not only for the development of metabolic syndrome but also for many cancers, including pancreatic ductal adenocarcinoma (PDAC). PDAC is the third leading cause of cancer-related death, and 5-year survival of PDAC remains around 9% in the U.S. Obesity is a known risk factor for PDAC. Metabolic control and bariatric surgery, which is an effective treatment for severe obesity and allows massive weight loss, have been shown to reduce the risk of PDAC. It is therefore clear that elucidating the connection between obesity and PDAC is important for the identification of a novel marker and/or intervention point for obesity-related PDAC risk. In this review, we discussed recent progress in obesity-related PDAC in epidemiology, mechanisms, and potential cancer prevention effects of interventions, including bariatric surgery with preclinical and clinical studies.

Butyrate Drives Metabolic Rewiring and Epigenetic Reprogramming in Human Colon Cancer Cells.

Butyrate (B) is a short-chain fatty acid produced by dietary fiber, known to inhibit histone deacetylases (HDACs) and possess cancer-preventive/anticancer effects. However, the role of B in metabolic rewiring, epigenomic reprogramming, transcriptomic network, NRF2 signaling, and eliciting cancer-preventive effects in colorectal cancer (CRC) HCT116 cell remains unclear. Sodium butyrate (NaB) dose-dependently inhibits the growth of CRC HCT116 cells. NaB inhibits NRF2/NRF2-target genes and blocks NRF2-ARE signaling. NaB increases NRF2 negative regulator KEAP1 expression through inhibiting its promoter methylation. Associative analysis of DEGs (differentially expressed genes) from RNA-seq and DMRs (differentially methylated regions) from CpG methyl-seq identified the tumor suppressor gene ABCA1 and tumor promote gene EGR3 are correlated with their promoters' CpG methylation indicating NaB regulates cancer markers through modulating their promoter methylation. NaB activated the mitochondrial tricarboxylic acid (TCA) cycle while inhibited the methionine metabolism which are both tightly coupled to the epigenetic machinery. NaB regulates the epigenetic enzymes/genes including DNMT1, HAT1, KDM1A, KDM1B, and TET1. Altogether, B's regulation of metabolites coupled to the epigenetic enzymes illustrates the potential underlying biological connectivity between metabolomics and epigenomics. B regulates KEAP1/NRF2 signaling, drives metabolic rewiring, CpG methylomic, and transcriptomic reprogramming contributing to the overall cancer-prevention/anticancer effect in the CRC cell model.

Cysteinyl Leukotriene Receptor Antagonists Associated With a Decreased Incidence of Cancer: A Retrospective Cohort Study.

AimCysteinyl leukotrienes receptor antagonists (LTRAs) are promising chemoprevention options to target cysteinyl leukotriene signaling in cancer. However, only a number of randomized clinical trials (RCTs) or observational studies have been conducted to date; thus, the effect of LTRAs on patients is yet to be elucidated. Using insurance claim data, we aimed to evaluate whether LTRAs have cancer preventive effects by observing patients who took LTRAs.MethodPatients diagnosed with asthma, allergic rhinitis, chronic cough, and have no history of cancer were followed-up from 2005 to 2017. Cox proportional hazard regression analysis was conducted to estimate the hazard ratios (HRs) for cancer risk of LTRA users.ResultWe followed-up (median: 5.6 years) 188,906 matched patients (94,453 LTRA users and 94,453 non-users). LTRA use was associated with a decreased risk of cancer (adjusted HR [aHR] = 0.85, 95% confidence interval [CI] = 0.83–0.87). The cancer risk showed a tendency to decrease rapidly when LTRAs were used in high dose (aHR = 0.56, 95% CI = 0.40–0.79) or for longer durations of more than 3 years (aHR = 0.68, 95% CI = 0.60–0.76) and 5 years (aHR = 0.33, 95% CI = 0.26–0.42). The greater preventive effects of LTRAs were also observed in patients with specific risk factors related to sex, age, smoking, and the presence of comorbidities.ConclusionIn this study, we found that LTRA use was associated with a decreased risk of cancer. The high dose and long duration of the use of LTRAs correlated with a lower cancer risk. Since LTRAs are not yet used for the prevention or treatment of cancer, our findings could be used for developing a new chemo-regimen or designing feasible RCTs.

Assessment of cancer prevention effect of exercise.

There are many documents about benefits of exercise on human health. However, evidences indicate to positive effect of exercise on disease prevention, understanding of many aspects of this mechanism need more investigations. Determination of critical genes which effect human health.GSE156249 including 12 gene expression profiles of healthy individual biopsy from vastus lateralis muscle before and after 12-week combined exercise training intervention were extracted from gene expression omnibus (GEO) database. The significant DEGs were included in interactome unit by Cytoscape software and STRING database. The network was analyzed to find the central nodes subnetwork clusters. The nodes of prominent cluster were assessed via gene ontology by using ClueGO. Number of 8 significant DEGs and 100 first neighbors analyzed via network analysis. The network includes 2 clusters and COL3A1, BGN, and LOX were determined as central DEGs. The critical DEGs were involved in cancer prevention process.

Cancer Prevention Effects of Foods, Food Groups, Nutrients, and Their Underlying Mechanisms

Cancer Prevention Effects of Foods, Food Groups, Nutrients, and Their Underlying Mechanisms

Autophagy-inducing nutritional interventions in experimental and clinical oncology.

Numerous pro-autophagic dietary interventions are being investigated for their potential cancer-preventive or therapeutic effects. This applies to different fasting regimens, methionine restriction and ketogenic diets. In addition, the supplementation of specific micronutrients such as nicotinamide (vitamin B3) or spermidine induces autophagy. In humans, leanness, plant-based diets (that may lead to partial methionine restriction) and high dietary uptake of spermidine are associated with a low incidence of cancers. Moreover, clinical trials have demonstrated the capacity of nicotinamide to prevent non-melanoma skin carcinogenesis. Multiple interventional trials are evaluating the capacity of autophagy-inducing regimens to improve the outcome of chemotherapy and immunotherapy. Here, we discuss the mechanistic underpinnings of autophagy induction by nutritional interventions, as well as the mechanisms through which autophagy induction in malignant or immune cells improves anticancer immunosurveillance.

The Role of Probiotics in Alzheimer’s Disease

Alzheimer’s disease (AD) is a chronic and progressive neurodegenerative disease that starts slowly and gradually worsens over the time and further leads to cognitive impairment and causes dementia. Since it is the most common neurodegenerative disease in older adults, no successful treatment has been reported. However, many studies in AD are associated with gut microbial alterations. Probiotics are living microorganisms that provide health benefits when consumed in the proper amount. Some probiotic strains provide health benefits such as improving the intestinal environment, immunomodulatory functions, prevention of infections, anti-obesity effects, cancer-preventing effects, and extension of life span.In contrast, some probiotic strains ameliorate cognitive impairment, CNS behavior, and depressive disorder. In many studies, probiotics have shown preventive and therapeutic potential in the case of AD. This review article aims to give a complete analysis of the role of probiotics in AD symptoms.