SCOPE:There are growing interests in using a whole-food-based approach to prevent chronic diseases due to potential synergistic interactions among different bioactive components within the whole foods. North American cranberry (Vaccinium macrocarpon), a polyphenol-rich fruit, has been shown to exert multiple beneficial health effects.METHODS AND RESULTS:For the first time, the protective effects of whole cranberry powder (WCP) are determined against colitis-associated mouse colon tumorigenesis induced by azoxymethane (AOM) and dextran sulfate sodium (DSS). The results show that dietary administration of WCP (1.5%, w/w in the diet) significantly suppresses colon tumorigenesis as indicated by the reduced tumor incidence, multiplicity, burden, and average tumor size in WCP-fed mice compared to the positive control mice. Both gene and protein expression levels of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α are markedly attenuated by WCP treatment in the colon of AOM/DSS-treated mice. Moreover, WCP profoundly modulates multiple signaling pathways/proteins related to inflammation, cell proliferation, apoptosis, angiogenesis, and metastasis in the colon, which is closely associated with the inhibitory effects of WCP on colon tumorigenesis.CONCLUSION:Overall, the results demonstrate chemopreventive effects of WCP on colon tumorigenesis in mice, providing a scientific basis for using the whole cranberry as a functional food to promote colon health in humans.

Introduction: Oral cancer is considered to be a global pandemic. The study was conducted to assess the anti-cancer activities of Chlorhexidine (CHX) and Cranberry against oral cancer cell lines. Material and Methods: Anticancer activity of CHX and Cranberry extract (CE) was assessed against AW13516 (poorly to moderately differentiated squamous cell carcinoma of tongue) and KB (Nasopharyngeal carcinoma) using Sulforhodamine B (SRB) assay at the Advanced Centre for Treatment Research and Education in Cancer (ACTREC) Mumbai, India. Three dose related parameters GI50, TGI and LC50 were calculated for each drug. Results: CE (80micro g/ml) showed no anti-cancer property against AW13516 cell line; however it showed 70.6% growth inhibition against KB cell line. CHX demonstrated 80.15% & 95.7% of growth inhibition against AW13516 & KB cell line respectively. Both the drugs were less potential than positive control drug Adriamycin, as reflected by their GI50, TGI and LC50 values. Conclusion: CHX exhibited better anti-cancer properties than CE for both the oral cancer cell lines.

It is increasingly perceived that dietary components have been linked with the prevention of intestinal cancer. Cranberry is a rich source of phenolic constituents and non-digestible fermentable dietary fiber, which shows anti-proliferation effect in colorectal cancer cells. Herein, we investigated the efficacy of long-term cranberry diet on intestinal adenoma formation in Apcmin/+ mice. Apcmin/+ mice were fed a basal diet or a diet containing 20% (w/w) freeze-dried whole cranberry powder for 12 weeks, and the number and size of tumors were recorded after sacrifice. Our results showed that cranberry strongly prevented the growth of intestinal tumors by 33.1%. Decreased cell proliferation and increased apoptosis were observed in tumors of cranberry-fed mice. Cranberry diet reduced the expression profile of colonic inflammatory cytokines (IFN-gamma, IL-1beta and TNF-alpha) accompanied with increased levels of anti-inflammatory cytokines (IL-4 and IL-10). Moreover, the number of colonic goblet cells and MUC2 production were increased, and the intestinal barrier function was also improved. In addition, cranberry diet increased caecal short chain fatty acids concentrations, and down-regulated epidermal growth factor receptor signaling pathway. These data firstly show the efficacy and associated mechanisms of cranberry diet on intestinal tumor growth in Apcmin/+ mice, suggesting its chemopreventive potential against intestinal cancer.

Cancer is one of the leading causes of deaths worldwide. The agents capable of causing damage to genetic material are known as genotoxins and, according to their mode of action, are classified into mutagens, carcinogens or teratogens. Genotoxins are involved in the pathogenesis of several chronic degenerative diseases including hepatic, neurodegenerative and cardiovascular disorders, diabetes, arthritis, cancer, chronic inflammation and ageing. In recent decades, researchers have found novel bioactive phytocompounds able to counteract the effects of physical and chemical mutagens. Several studies have shown potential antigenotoxicity in a variety of fruits. In this review (Part 1), we present an overview of research conducted on some fruits (grapefruit, cranberries, pomegranate, guava, pineapple, and mango) which are frequentl consumed by humans, as well as the analysis of some phytochemicals extracted from fruits and yeasts which have demonstrated antigenotoxic capacity in various tests, including the Ames assay, sister chromatid exchange, chromosomal aberrations, micronucleus and comet assay.

Breast cancer is the most common cancer and a major cause of death in women. The present study was designed to evaluate the antioxidant and anticancer potential of cranberry extract against N-methyl-N-nitrosourea (MNU) induced mammary carcinoma in rats. The tumor was induced in Female virgin rats of age 50 days by single dose of MNU (50mg/kg.b.w i.p.). After 85 days; all rats developed at least one tumor. Animals were treated with cranberry extract (400 and 600 mg/kg.b.w.orally) and tamoxifen (2mg/kg.b.w. i.p) for 4 weeks (from day 86 to day 113). MNU treatment resulted in a significant decrease (p < 0.05) in blood hemoglobin (Hb), red blood cells (RBC), platelets (PLTs) as well as blood, liver and breast catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD). However, MNU treatment resulted in a significant increase in White blood cells (WBC) as well as plasma, liver and mammary tissue gamma glutamyl transferase (GGT), lactate dehydrogenase (LDH), hexosamine, sialic acid and thiobarbituric acid reactive substances (TBARs). Upon administration of the cranberry extract, the levels of WBC, GGT, LDH, hexosamine, sialic acid, TBARs, Hb, RBC, PLTs, CAT, GPx and SOD were significantly normalized. Histopathological changes also confirmed the formation of tumor tubules and neovascularization after the MNU treatment. Cranberry extract administration significantly reduces the growth of MNU-induced mammary tumors, and therefore has strong potential as a useful therapeutic regimen for inhibiting breast cancer development. Comparing the beneficial effect of cranberry extract with that of MNU-induced breast cancer, cranberry extract showed antitumor and antioxidant activity indicated by the measured biochemical parameters and the histopathological examination of mammary tissue. The results of the present study indicate that cranberry extract possesses strong anticancer effects through its role in modulating glycoprotein components and the levels of oxidative stress biomarkers. Cranberry exerted a stronger anticancer effect at the dosage of 600 mg/kg body weight than at dosage 400 mg/kg body weight.

Cranberries are rich in bioactive constituents reported to influence a variety of health benefits, ranging from improved immune function and decreased infections to reduced cardiovascular disease and more recently cancer inhibition. A review of cranberry research targeting cancer revealed positive effects of cranberries or cranberry derived constituents against 17 different cancers utilizing a variety of in vitro techniques, whereas in vivo studies supported the inhibitory action of cranberries toward cancers of the esophagus, stomach, colon, bladder, prostate, glioblastoma and lymphoma. Mechanisms of cranberry-linked cancer inhibition include cellular death induction via apoptosis, necrosis and autophagy; reduction of cellular proliferation; alterations in reactive oxygen species; and modification of cytokine and signal transduction pathways. Given the emerging positive preclinical effects of cranberries, future clinical directions targeting cancer or premalignancy in high risk cohorts should be considered.

Background and Objectives. Recently, we described an inverse association between cranberry supplementation and serum prostate specific antigen (PSA) in patients with negative biopsy for prostate cancer (PCa) and chronic nonbacterial prostatitis. This double blind placebo controlled study evaluates the effects of cranberry consumption on PSA values and other markers in men with PCa before radical prostatectomy. Methods: Prior to surgery, 64 patients with prostate cancer were randomized to a cranberry or placebo group. The cranberry group (n=32) received a mean 30 days of 1500 mg cranberry fruit powder. The control group (n=32) took a similar amount of placebo. Selected blood/urine markers as well as free and total phenolics in urine were measured at baseline and on the day of surgery in both groups. Prostate tissue markers were evaluated after surgery. Results: The serum PSA significantly decreased by 22.5% in the cranberry arm (n=31, P<0.05). A trend to down-regulation of urinary beta-microseminoprotein (MSMB) and serum gamma-glutamyltranspeptidase, as well as upregulation of IGF-1 was found after cranberry supplementation. There were no changes in prostate tissue markers or, composition and concentration of phenolics in urine. Conclusions: Daily consumption of a powdered cranberry fruit lowered serum PSA in patients with prostate cancer. The whole fruit contains constituents that may regulate the expression of androgen-responsive genes.

In the present study, anti-proliferative activities of cranberry derived flavonoids and some of their in vivo metabolites were evaluated using a panel of human bladder tumor cell lines (RT4, SCABER, and SW-780) and non-tumorigenic immortalized human uroepithelial cells (SV-HUC). Among the compounds tested, quercetin 3-O-glucoside, isorhamnetin (3'-O-methylquercetin), myricetin and quercetin showed strong concentration-dependent cell growth inhibitory activities in bladder cancer cells with IC50 values in a range of 8-92 micro M. Furthermore, isorhamnetin and myricetin had very low inhibitory activity against SV-HUC even at very high concentrations (>200 micro M) compared to bladder cancer cells, indicating that their cytotoxicity is selective for cancer cells. To determine whether the differential cell growth inhibitory effects of isomeric flavonoids quercetin 3-O-glucoside (active) and hyperoside (quercetin 3-O-galactoside) (inactive) are related to their metabolism by the cancer cells, SW-780 cells were incubated with these compounds and their metabolism was examined by LC-MS/MS. Compared to quercetin 3-O-glucoside, hyperoside undergoes relatively less metabolic biotransformation (methylation, glucuronidation and quinone formation). These data suggest that isorhamnetin and quercetin 3-O-glucoside may be the active forms of quercetin in prevention of bladder cancer in vivo and emphasize the importance of metabolism for the prevention of bladder cancer by diets rich in cranberries.

The present study was to evaluate anti-leukopenia and antioxidant effects of cranberry extract(222mg/kg.b.w, orally)in 400mg/kg.b.w., orally benzene and/or 20mg/kg.b.w., I.P 5-Flourouracil-induced leukopenia rats. Two weeks after induction of leukopenia in rats, cranberry extract was administrated for 30 consecutive days. Onthe31thday, the rats were sacrificed for the estimation of hemoglobin (Hb%), complete blood cell count Leucocyte (WBC) and platelet count (PLT),as well as biochemical parameters; alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), lipid peroxides (TBARS), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), total cholesterol (TC), triglycerides (TG), HDL-C, LDL-C, p53gene expression, nitric oxide (NO) and tumor necroses factor-alpha (TNF-alpha). The results of this study showed that administration of cranberry extract to leukopenia induced rats demonstrated a significant (P<0.01) increase in Hb%, WBCs and PLT as well as a significant (P<0.01) improvement in biochemical parameters and life span as compared to benzene and/or 5-Flourouracil control rats. The histological examinations of this study revealed damage and degeneration in the lung of benzene and/or 5-Flourouracil treated rats. Also, lung of cranberry treated rats showed significant improvement and protection against benzene and/or 5-Flourouracil harmful effect. On the other hand, the results clearly suggested that the oxidative stress of benzene was higher than 5-Flourouracil. Industrial relevance. Our observations have clearly demonstrated that the cranberry extract has significant antioxidant and anti-leukopenia activity due to presence of phenolic compounds. Cranberry extract possessed a capability to inhibit the lipid peroxidation and activate the antioxidant markers (GSH, SOD and CAT) in leukopenia-induced by 5-Flourouracil and benzene in rats. Also, industrial relevance of the present results showed that cranberry extract can be used as an antioxidant and anti-leukopenia therapeutic agent and deserves clinical trial in the near future as an adjuvant therapy in leukopenic patients. This could serve as a stepping stone towards the discovery of newer safe and effective antitumor agents.

Cranberries are rich in bioactive constituents known to improve urinary tract health and more recent evidence supports cranberries possess cancer inhibitory properties. However, mechanisms of cancer inhibition by cranberries remain to be elucidated, particularly in vivo. Properties of a purified cranberry-derived proanthocyanidin extract (C-PAC) were investigated utilizing acid-sensitive and acid-resistant human esophageal adenocarcinoma (EAC) cell lines and esophageal tumor xenografts in athymic NU/NU mice. C-PAC induced caspase-independent cell death mainly via autophagy and low levels of apoptosis in acid-sensitive JHAD1 and OE33 cells, but resulted in cellular necrosis in acid-resistant OE19 cells. Similarly, C-PAC induced necrosis in JHAD1 cells pushed to acid-resistance via repeated exposures to an acidified bile cocktail. C-PAC associated cell death involved PI3K/AKT/mTOR inactivation, pro-apoptotic protein induction (BAX, BAK1, deamidated BCL-xL, Cytochrome C, PARP), modulation of MAPKs (P-P38/P-JNK) and G2-M cell cycle arrest in vitro. Importantly, oral delivery of C-PAC significantly inhibited OE19 tumor xenograft growth via modulation of AKT/mTOR/MAPK signaling and induction of the autophagic form of LC3B supporting in vivo efficacy against EAC for the first time. C-PAC is a potent inducer of EAC cell death and is efficacious in vivo at non-toxic behaviorally achievable concentrations, holding promise for preventive or therapeutic interventions in cohorts at increased risk for EAC, a rapidly rising and extremely deadly malignancy.