Cancer Preventive Properties Research Articles

Characterization of Cistus × incanus L. and Cistus ladanifer L. Extracts as Potential Multifunctional Antioxidant Ingredients for Skin Protecting Cosmetics.

Skin is constantly exposed to harmful environmental factors, causing photo-oxidative stress in cells and leading to the development of health and aesthetic problems. Multifunctional ingredients of everyday skincare products, possessing antioxidant, UV-protecting, anti-hyperpigmentation, and skin cancer-preventing properties are in high demand. Due to the high content of polyphenolic compounds Cistus × incanus L. and Cistus ladanifer L. are potentially interesting sources of cosmetic ingredients with multiple skin protecting functions. In this study eight extracts from dried C. incanus and C. ladanifer—aerial parts were prepared using 60% (v/v) or 100% (v/v) methanol, on a magnetic stirrer or in Soxhlet apparatus, and compared for their content of phytochemicals and properties important for the skin protection. Extracts from C. incanus prepared in 60% (v/v) methanol contained the highest amount of polyphenolic compounds (331.82–347.27 mg GAE/g DW) and showed the most significant antioxidant activity (IC50 = 3.81–4.05 µg/mL). C. incanus extracts were also effective tyrosinase inhibitors (30–70% inhibition at 100 µg/mL). Statistical correlation analysis revealed that epicatechin, epigallocatechin gallate (EGCG), and myricitrin may be responsible for the antioxidant and tyrosinase inhibitory potential of C. incanus extracts. All analyzed extracts were cytotoxic for human melanoma cells A375 (IC50 = 57.80–199.01 µg/mL), with C. incanus extract prepared in 100% (v/v) methanol using Soxhlet extraction being the most effective. The extracts did not significantly impair the growth of noncancerous human keratinocytes HaCaT. C. incanus and C. ladanifer extracts possess also natural sun protecting activity (SPF 3.42–3.77 at 100 µg/mL), enhancing their anti-hyperpigmentation and anti-melanoma potential.

Effects of Green Tea and Black Tea on Salivary pH and Flow Rate in Healthy Individuals

Introduction: Saliva is a complex fluid secreted by salivary glands that functions to provide lubrication for chewing, swallowing, and aids in digestion. It also helps to maintain the oral health by protecting against microbial invasion that may lead to oral disease. Green tea and black tea has been reported to have anti-oxidant, anti-diabetic and other health benefits, hence we aimed to study the effect of green tea and black tea on salivary pH and flow rate which has significant role in oral health. Materials and methods: A total of 60 students between the ages of 18 to 23 years were included in the study. The students were divided into two groups as green tea group (Group G) and black tea group (Group B). Saliva samples were collected before and after rinsing with black tea and green tea. The collected saliva was used for estimation of salivary pH and flow rate. Results: In our study there was statistical significant increase in the pH of saliva before and after rinsing with black tea. Also there was statistical significant increase in the saliva flow rate before and after rinsing in both black tea and green tea respectively. On comparison between the green tea and black tea group, there was statistical significant increase in pH (p<0.001) in black tea group. Conclusion: Green tea and black tea have beneficial effect on systemic and oral health through its antioxidant, anti-inflammatory, antibacterial, anti-cariogenic and cancer-preventive properties. The present study demonstrates an increase in salivary pH and flow rate on rinsing with black tea compared to green tea.

The Ability of Ginger Rhizome (Zingiber officinale Rosc) Extract in Producing of Silver Nanoparticles and the Antibacterial activity of these nanoparticles

Recently, using plant extract as a reducing agent for nanosilver particle synthesis hasbeen focused. This is a green technology utilizing the ready material in the nature to create thenanoparticles with good properties and uniqe quality. In this study, ginger rhizome extract wasused to reduce the silver cation (Ag + ) to silver (Ag o ) as nanoparticles with uniqe quality and evendistribution in the solution. The size of the particles varied in the range of 20-40 nm. Reactionconditions were investigated and optimized with AgNO 3 concentration of 3mM, extractsolution/AgNO 3 solution of 1/5, temperature of 80˚C, pH of 12 and reaction time of 30 min. Theresults obtained from the antibacterial assays showed that silver nanoparticle solution hadantibacterial ability with an average effective diameter of 10 mm. It also indicated that theantibacterial activity of silver nanoparticle solution on the Gram (-) bacterium (E. coli) is betterthat on Gram (+) bacterium (S. aureus). In conclusion, we suggest that the ginger rhizome extractcan be used to produce silver nanoparticles in mild reaction conditions; the silver nanoparticlesolution expressed as a quite good antibacterial agent and therefore could be applied in decreasingthe effects of deleterious bacteria.Keywords&#x0D; Silver nanoparticle, plant extract, antibacterial, Zingiber officinale Rosc.&#x0D; References&#x0D; [1] L.S. Li, J. Hu, W. Yang and P. Alivisatos. Band gap variation of size- and shape-controlled colloidal CdSe quantum rods. Nano Lett. 1(2001) 49-51. https://doi.org/10.1021/nl015559r.[2] A. P. Nikalje. Nanotechnology and its Applications in Medicine. Medicinal chemistry, 5(2015) 81-89.[3] G. Doria, J. Conde, B. Veigas et al. Noble metal nanoparticles for biosensing applications. Sensors 12(2012) 1657–1687. https://doi.org/ 10.4172/2161 -0444.1000247[4] A. J. Haes, A. D. McFarlan, R. P. van Duyne. Nanoparticle optics: sensing with nanoparticle arrays and single nanoparticles. 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Energy transfer mechanisms in pH-tuned aggregates of curcumin.

Curcumin ((1,7-bis-(4-hidroxi-3-metoxifenil)-1,6-heptadieno-3,5-diona)), is a natural yellow-orange polyphenol dye, obtained from Curcuma longa rhizomes, with vast potential in the biotechnology field, such as anti - inflammatory and cancer preventive properties, and a very environmental-sensible structure, mostly resulting in aggregate formations, with low solubility in aqueous solvents and remarkable pH dependence. Hence, it is essential to comprehend its aggregation mechanisms, optical properties and conformational equilibrium to develop curcumin-based drugs and biomaterials for several applications. With the purpose of understand such concepts and its properties, the results presented in this work, obtained through spectroscopic measurements and the Hill's modeling, show a conformational equilibrium, driven by pH, between the enol-enolate and aggregated forms in curcumin, and the respective energy transfer processes between these species. Additionally, the photophysical mechanisms for the energy transfer between aggregated forms, observed with the ellipsometry measurements, showed an "all-or-nothing" character, pointing to a very complex conformation for curcumin aggregates.

Mushroom polysaccharides and jiaogulan saponins exert cancer preventive effects by shaping the gut microbiota and microenvironment in ApcMin/+ mice

The incidence of colorectal cancer (CRC) is alarming among younger peoples. While no effective chemopreventive drug available in the market, researchers have been searching for alternative strategies against CRC that are in demand. Therefore, we tested the cancer-preventive properties of Ganoderma lucidum (Lingzhi) polysaccharides (GLP), along with the saponins extracted from Gynostemma pentaphyllum (GpS), an herbal tea with prebiotic-like effects. Here, we report that saponins from Gynostemma pentaphyllum (GpS) and polysaccharides from Ganoderma lucidum (GLP together with GpS) profoundly improved the inflamed gut barrier of ApcMin/+ mice by reducing polyps, shifting colonic M1 to M2 macrophages, positively reverting E-cadherin/N-cadherin ratio, and downregulating oncogenic signaling molecules. The treatments also markedly promoted short-chain fatty acids (SCFAs)˗producing bacteria and abridged sulfate-reducing bacteria in a time-dependent manner. G-protein coupled-receptors were significantly stimulated in the treated mice, accompanied by the modulated expressions of histone deacetylases, anti-cancer gut hormone PYY, and PPAPγ. These findings suggest that some of the herbal medicinal foods could modulate the relationship between the host and the gut microbiota (GM) to exert their beneficial properties to the host. Our study also implicates that these dietary mushroom polysaccharides and the Gp saponins have the potential to be developed as new preventive medicines against CRC.

Evaluation of oxidative stress in patients of follicular thyroid cancer and study the therapeutic effect of Resveratrol on oxidative stress in FTC-133 thyroid cancer cell line

The second most common cancer of the Thyroid gland is FollicularThyroid Carcinoma (FTC), second only to papillary carcinoma. Resveratrol, a natural polyphenolic compound that has anti- oxidative, anti-inflammatory and apoptotic properties, appears to have substantial cardio protection and cancer-prevention properties. Furthermore, resveratrol is thought to be responsible for regulating several biological processes, such as metabolism and aging, through the modulation of the mammalian silent information regulator 1 (SIRT1) of the Sirtuins family. The purpose of this study is evaluating erythrocyte malondialdehyde’s (MDA) role in the indication of the oxidative status in follicular thyroid carcinoma patients and investigating the therapeutic effect of resveratrol, a potent antioxidant, upon oxidative stress levels in thyroid cancer in vitro.Malondialdehyde was evaluated in erythrocyte of follicular thyroid cancer patients after and before treatment with sodium stibogluconate .Cytotoxicity by MTT assay and intracellular reactive oxygen species (ROS) levels was measured after resveratrol treatment on follicular thyroid carcinoma FTC-133 cell line. The results of this study confirmed that150 μM Resveratrol inhibited proliferation of FTC-133 thyroid cancer cell line in vitro by 88% after 72hand treatment with 50-200μM Resveratrol reduced ROS levels.To sum up,considering its mode of action, resveratrol might have an important role providing a source for natural antitumor agents, a fact that would have great therapeutic potential in integrated oncology.

Abstract 5091: Inhibition of mutagenicity of 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine ( PhIP) by aqueous extract (crude) and organic extract (pulegone) of Calamintha nepeta.

Abstract Inhibition of mutagenicity of 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) by aqueous extract (crude) and organic extract (pulegone) of Calamintha nepeta. Calamintha nepeta (CN) is an aromatic mint used as a traditional medicinal herb in Europe and the Mediterranean for its broad range of biological activities; these include anti-inflammatory, antioxidant, antimicrobial, anti-ulcer, insecticidal, and cancer-preventive properties. Previous studies have revealed the apoptotic and cancer-preventing attributes of its major organic fractions: pulegone (PUL, 2760 ppm), D-limonene (385 ppm), and menthone (590 ppm). PUL (6.4 - 800 mg/plate) was not mutagenic in Salmonella typhimurium TA97, TA98, TA100, TA1535, or TA1537 regardless of S9 metabolic activation. When cooking at high temperatures, creatine, sugars, and amino acids begin to produce 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), which yielded positive results in the Ames mutagenicity tests. PhIP is one of the most abundant heterocyclic amines (HCAs) in cooked meat and the U.S. Department of Health and Human Services’ National Toxicology Program has denounced it as "reasonably anticipated to be a human carcinogen". Thus, cancer of the prostate, breast, lung, esophagus, stomach, and colorectal may be related to high intake and high exposure to PhIP. This study assessed and compared the effects of total aqueous and organic extracts of CN on PhIP-induced mutagenesis using TA98 as the bacterial tester strain and rat liver 9000 x g supernatant (S9) as the metabolic activation system. Our results showed that both the crude aqueous extract and organic essential oil extract (PUL) of the herb significantly inhibited the mutagenicity of PhIP (both 0.1 and 1 µg/plate), bioactivated by S9 (800 mg/plate), in a dose-response fashion (p &amp;lt; 0.05). The percent inhibition of revertant formation for these two extracts against 0.1 µg/plate of PhIP were: 32%, 74%, 79%, 84%, and 90% regarding the total aqueous extract (0.1, 0.5, 1.0, 1.5, and 3 mg/plate) and 28%, 36%, 64%, 75%, and 97% for the PUL essential oil of the organic extract (1.0, 10, 50, 100, and 200 µg/plate). Both the aqueous and organic extracts revealed the same trend of significance (p &amp;lt; 0.05) concerning percent inhibition of revertant formation against PhIP (1 µg/plate) in a dose-response fashion. The organic fraction (PUL) maintained a stronger antimutagenic effect in comparison to the total aqueous effect. These results suggest that both aqueous crude extract and organic PUL extract of CN contain antimutagenic phytochemicals concerning PhIP-induced mutagenicity. Further study of their modulatory effects on metabolism and the DNA binding of PhIP is warranted to reveal the potential antimutagenicity mechanism and their chemopreventive properties against PhIP and potentially against other HCAs. Citation Format: Yanlingxue Wan, Ryan Hayes, Joshua Li, Kristin Ferrer, Padma T. Uppula, Brian Yuen Yau Wong. Inhibition of mutagenicity of 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine ( PhIP) by aqueous extract (crude) and organic extract (pulegone) of Calamintha nepeta. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5091.

Natural and Synthetic Isothiocyanates Possess Anticancer Potential Against Liver and Prostate Cancer In Vitro.

Isothiocyanates (ITCs) are phytochemicals with potential cancer-preventative properties derived from the breakdown of glucosinolates that exist in cruciferous vegetables. Studies, to date, have demonstrated that various ITCs possess the ability to act as anticancer agents in different cancer types. This study investigated the anticancer properties of dietary ITCs (allyl-ITC, benzyl-ITC, phenylethyl-ITC) and synthetic (phenylbutyl-ITC and phenylhexyl-ITC) on liver and prostate carcinoma cells in vitro. The effects of ITCs on cellular viability, migration, invasion, clonogenicity, apoptosis induction and reactive oxygen species generation were assessed in HepG2, DU145 and 22Rv1 cells. All ITCs reduced metabolic activity in each cell line with the most significant being phenylethyl-ITC. Both dietary and synthetic ITCs suppressed the migratory and invasive potential of all cell lines, inhibited colony-forming capability and induced apoptosis. Phenylethyl-ITC exposure resulted in the significant generation of reactive oxygen species. These data highlight the potential advantages of utilizing ITCs to delay the carcinogenic process and the potential for dietary and synthetic ITCs to act as anticancer agents.

Structure, antiproliferative and cancer preventive properties of sulfated α-d-fucan from the marine bacterium Vadicella arenosi

Sulfated fucose-containing glycopolymers are currently of great interest because of their wide spectrum of bioactivity, including anti-tumor properties. In this study, the structure of O-polysaccharide (OPS) of the marine bacterium Vadicella arenosi KMM 9024T, its effect on the proliferation of human breast cancer MCF-7 cells and cancer preventive properties were investigated. Two OPS fractions with different molecular weights were isolated and purified from the lipopolysaccharide by mild acid hydrolysis followed by anion-exchange chromatography. The OPS was found to consist of α-(1→3)-linked 2-O-sulfate-d-fucopyranosyl residues, whose structure was deduced by sugar analysis along with 2D NMR spectroscopy. The biological assay indicated that polysaccharide significantly reduced the proliferation and inhibited colony formation of MCF-7 cells in a dose-dependent manner. Besides, the experiment indicated the inhibitory role of polysaccharide on EGF-induced neoplastic cell transformation in mouse epidermal cells. The investigated polysaccharide is the first sulfated fucan isolated from the bacteria.

Dying for a good night of sleep?: Researchers are investigating how poor sleep can increase the risk of cancer or worsen the course of the disease.

Dying for a good night of sleep?: Researchers are investigating how poor sleep can increase the risk of cancer or worsen the course of the disease.

Aspirin impairs acetyl-coenzyme A metabolism in redox-compromised yeast cells

Aspirin is a widely used anti-inflammatory and antithrombotic drug also known in recent years for its promising chemopreventive antineoplastic properties, thought to be mediated in part by its ability to induce apoptotic cell death. However, the full range of mechanisms underlying aspirin’s cancer-preventive properties is still elusive. In this study, we observed that aspirin impaired both the synthesis and transport of acetyl-coenzyme A (acetyl-CoA) into the mitochondria of manganese superoxide dismutase (MnSOD)-deficient Saccharomyces cerevisiae EG110 yeast cells, but not of the wild-type cells, grown aerobically in ethanol medium. This occurred at both the gene level, as indicated by microarray and qRT-PCR analyses, and at the protein level as indicated by enzyme assays. These results show that in redox-compromised MnSOD-deficient yeast cells, but not in wild-type cells, aspirin starves the mitochondria of acetyl-CoA and likely causes energy failure linked to mitochondrial damage, resulting in cell death. Since acetyl-CoA is one of the least-studied targets of aspirin in terms of the latter’s propensity to prevent cancer, this work may provide further mechanistic insight into aspirin’s chemopreventive behavior with respect to early stage cancer cells, which tend to have downregulated MnSOD and are also redox-compromised.

Simultaneous separation of six pure polymethoxyflavones from sweet orange peel extract by high performance counter current chromatography

Successful isolation of polymethoxyflavones (PMFs) from citrus peels has led to numerous evaluations of PMFs in a broad spectrum of biological activities, such as inhibition of chronic inflammation, cancer prevention and anti-atherogenic properties. Recent reports associated with the health promoting properties of PMFs in citrus fruits have dramatically increased. However, the limiting factor in animal and human study of PMFs is still the supply of pure PMFs, such as tangeretin, nobiletin, sinensetin and 3,5,6,7,3′,4′-hexamethoxyflavone. Herein, we introduce the newly developed efficient separation method using high-performance counter-current chromatography (HPCCC) in isolating multiple pure single PMFs simultaneously in one cycle process. With the smallest preparation loop on the semi-preparative HPCCC instrument, the optimized solvent system of hexanes/ethyl acetate/methanol/water resulted in the isolation of pure sinensetin, tangeretin, nobiletin, 3,5,6,7,3′,4′-hexamethoxyflavone, 5,6,7,4′-tetramethoxyflavone and 3,5,6,7,8,3′,4′-heptamethoxyflavone directly from crude sweet orange peel extract in one cycle of separation process by HPCCC in the mode of reverse phase. The purity of each of the six isolated PMFs is greater than 96.6% analyzed by high-performance liquid chromatography and proton nuclear magnetic resonance. Scale-up and high purity of individual PMFs can be separated by using a large separation loop in preparative HPCCC model. The renovated HPCCC methodology can be practically used in natural product isolation and consequent biological property evaluation.

Anti-inflammatory activity of synthetic and natural glucoraphanin

Glucoraphanin is one of the best known glucosinolates because of its health benefits. The compound is known to eliminate carcinogens in tissue and hence is frequently studied for its cancer preventative properties. In this work, the total synthesis of ?- and ?-glucoraphanin epimers was attempted. ?-Glucoraphanin potassium salt was successfully synthesized in high overall yield, whereas the ?-epimer was found to be unstable as it decomposed in the final step of the total synthesis. The anti-inflammatory activity of the synthetic glucoraphanin was determined by inhibition of the release of tumor necrosis factor alpha (TNF-?) secretion in lipopolysaccharide-stimulated THP-1 cells. It was shown that in the presence of either the synthetic or natural glucoraphanin, TNF-? secretion was significantly reduced (?52 % inhibition) at a concentration of 15 ?M.

Genistein Affects Expression of Cytochrome P450 (CYP450) Genes in Hepatocellular Carcinoma (HEPG2/C3A) Cell Line.

Background: Genistein (5,7-Dihydroxy-3-(4-hydroxyphenyl)-4H-1-benzopyran-4-one) is the most abundant isoflavone in soybean, which has been associated with a lower risk of development of cancer and cardiovascular diseases. Of particular interest regarding cancer preventive properties of flavo-noids is their interaction with cytochrome P450 enzymes (CYPs). However, contradictory data report the effect of genistein on expression of СYPs enzymes.Objective: The aim of this study was to investigate the effects of genistein on cytochrome P450 (CYP) gene expression levels in human hepatocellular carcinoma (HepG2/C3A) and colon adenocarcinoma (HT29) cells.Methods: Real-time RT–PCR was used to examine the expression of genes families involved in xenobi-otic metabolism, such as CYP1 (CYP1A1, CYP1B1), CYP2 (CYP2E1, CYP2D6), CYP3 (CYP3A4); and of a family involved in the catabolism of the all-trans-retinoic acid (ATRA), CYP26 (CYP26A1, CYP26B1).Results: RT-qPCR data analysis showed that after 12 h of exposure of HepG2/C3A cells to genistein (5 and 50 µM) there was an upregulation of CYP1A1 and CYP1B1 and downregulation of CYP2D6, CYP26A1 and CYP26B1 mRNA levels. There was no change in the mRNA levels of CYP P450 genes in HT29 cells.Conclusion: Our results suggest that treatment with genistein in non-toxic concentrations may impact the expression level of CYPs involved in the biotransformation of xenobiotics and drug metabolizing en-zymes. Moreover, the downregulation of ATRA metabolism-related genes opens a new research path for the study of genistein as retinoic acid metabolism blocking agent for treating cancer and other patholo-gies.

Determination of indole-type phytonutrients in cruciferous vegetables

Consumption of cruciferous vegetables has been associated with a low risk of developing cancer. Indole-type phytonutrients, derived from enzymatic hydrolysis of glucobrassicin, exhibit cancer-preventive properties and occur in all vegetables of the Brassicaceae family. A LC-Q-TOF-MS methodology was developed and applied in extracts from seven cruciferous vegetables allowing the rapid determination of indole-3-carbinol, indole-3-carbaldehyde, ascorbigen, indole-3-acetic acid and indole-3-acetonitrile. The novel method described herein, was validated and is characterized by low detection limits and excellent linearity. The simultaneous determination of indole-type phytonutrients in turnip and radish was performed for the first time.

227 - Neuroprotective efficacy of curcumin in lead (Pb) induced inflammation and cholinergic dysfunction in mice

Curcumin from the rhizomes of Curcuma longa has many pharmacological activities including antioxidant, anti-inflammatory and cancer preventive properties. This study was designed to assess the protective effect of Curcumin against lead induced neurotoxicity. ICR mice were exposed to lead acetate (Pb) in drinking water (1%) with or without orally administrated Curcumin (100 and 200 mg/kgBW) and Vitamine E, the antioxidant positive control, once daily for 38 days. The results exhibited that Curcumin significantly protected against Pb induced learning deficit and memory loss in a concentration dependent manner, indicated by Water maze swimming test and Forced depression test. Pb induced a profound alteration of circulating Tumor necrosis factor-α (TNF-α), alteration inflammatory markers, TNF-α, COX-2 and iNOS, and elevation of oxidative damage, as evidenced by increasing lipid peroxide (malondialdehyde, MDA) levels in blood and brain tissues of mice as found in mice-treated with Vitamine E. The toxic effects of Pb may be mitigated by Curcumin and Vitamine E due to ameliorated inflammatory markers and increased expression of ChAT and AChE proteins lead to increased AChE activity in the brain compared to Pb alone, as shown by Western blot analysis. Taken together, these results suggested that Curcumin significantly alleviates Pb induced neurotoxicity, at least in part, by suppression inflammation, oxidative damage, alteration in neurotransmitter and enzyme expression (AChE and ChAT) with a reduction learning deficit and memory loss.

Metabolic Profiles Associated With Metformin Efficacy in Cancer

Metformin is one of the most commonly prescribed medications for the treatment of type 2 diabetes. Numerous reports have suggested potential anti-cancerous and cancer preventive properties of metformin, although these findings vary depending on the intrinsic properties of the tumor, as well as the systemic physiology of patients. These intriguing studies have led to a renewed interest in metformin use in the oncology setting, and fueled research to unveil its elusive mode of action. It is now appreciated that metformin inhibits complex I of the electron transport chain in mitochondria, causing bioenergetic stress in cancer cells, and rendering them dependent on glycolysis for ATP production. Understanding the mode of action of metformin and the consequences of its use on cancer cell bioenergetics permits the identification of cancer types most susceptible to metformin action. Such knowledge may also shed light on the varying results to metformin usage that have been observed in clinical trials. In this review, we discuss metabolic profiles of cancer cells that are associated with metformin sensitivity, and rationalize combinatorial treatment options. We use the concept of bioenergetic flexibility, which has recently emerged in the field of cancer cell metabolism, to further understand metabolic rearrangements that occur upon metformin treatment. Finally, we advance the notion that metabolic fitness of cancer cells increases during progression to metastatic disease and the emergence of therapeutic resistance. As a result, sophisticated combinatorial approaches that prevent metabolic compensatory mechanisms will be required to effectively manage metastatic disease.

Resveratrol promotes oxidative stress to drive DLC1 mediated cellular senescence in cancer cells

Induction of cellular senescence represents a novel strategy to inhibit aberrant proliferation of cancer cells. Resveratrol is gaining attention for its cancer preventive and suppressive properties. Tumor suppressor gene DLC1 is shown to induce apoptosis, suppress migration and invasion in various cancer cells. However, the function of DLC1 in cancer cellular senescence is unclear. This study was designed to investigate the biological role of DLC1 in resveratrol induced cancer cellular senescence. Our results showed that resveratrol inhibited proliferation of cancer cell lines (MCF-7, MDA-MB-231 and H1299) and induced senescence along with increase of SA-β-gal activity and regulation of senescence-associated molecular markers p38MAPK, p-p38MAPK, p27, p21, Rb and p-Rb protein. The underlying mechanism was that resveratrol induced mitochondrial dysfunction with reduction of mitochondrial membrane potential, down-regulation of MT-ND1, MT-ND6 and ATPase8 in transcript level and down-regulation of PGC-1α in protein level to result in ROS production. With ROS elevation, resveratrol decreased DNMT1 and increased DLC1 expression significantly. However, after ROS scavenger NAC was added to the cancer cells treated by resveratrol, DNMT1, DLC1 and senescence-associated molecular markers were reversed. This reveals that resveratrol induced cancer cellular senescence through DLC1 in a ROS-dependent manner. Silencing DLC1 markedly attenuated SA-β-gal activity and p38MAPK, p27 and p21 protein levels, and increased Rb expression, indicating that resveratrol promoted senescence via targeting DLC1. Moreover, DLC1 promoted senescence through FoxO3a/NF-κB signaling mediated by SIRT1 after resveratrol treatment. Finally, resveratrol increased ROS production to induce DNA damage with p-CHK1 up-regulation and result in cancer cellular senescence. This is the first time to investigate resveratrol induced cancer cellular senescence by primarily targeting DLC1. Induction of cellular senescence by resveratrol may represent a novel anticancer mechanism.

Influence of vitamin D (Vit D) on mammographic density (MD) and insulin like growth factor 1 (IGF1): Results of CALGB (Alliance) 70806.

1549Background: Vitamin D is safe and has breast cancer prevention properties. CALGB 70806 was a randomized phase II trial evaluating the effect of vit D on several breast cancer biomarkers (includ...

Effect of Saccharomyces Boulardii Cell Wall Extracts on Colon Cancer Prevention in Male F344 Rats Treated with 1,2-Dimethylhydrazine

ABSTRACTThe effect of Saccharomyces boulardii cell wall extracts on colon cancer prevention in rats treated with 1,2-dimethylhydrazine was investigated. A crude insoluble glucan (0.5 and 1.0 mg/kg/day) and a crude mannoprotein extract (0.3 and 3.0 mg/kg/day) were administered in rats by gavage for 12 weeks along with a high fat low fiber diet whereupon rats were sacrificed and aberrant crypt foci (ACF) were counted in the colon. Moreover, NAD(P)H: quinone reductase (QR) and harmful fecal enzymes (β-glucosidase and β-glucuronidase) were quantified in the liver and in the caecum, respectively. Results showed a reduction in ACF counts, a decreased β-glucuronidase activity and an increased QR activity when rats were treated only with insoluble glucan. While these enzymatic modulations may be constituted one of the mechanisms that is responsible for the reduction of ACF counts observed, the reduction of ACF counts caused by insoluble glucan should be addressed, at least, as a biomarker of their cancer-prevention properties. To our knowledge, this is the first study demonstrated that crude cell wall extract obtained from S. boulardii could have a potential role in colon cancer prevention in vivo by revealing the potential implication of QR and β-glucuronidase modulation.