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Oncology/Anti-Cancer

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Cranberry Extract as a Supplemented Food inTreatment of Oxidative Stress and Breast Cancer Induced by n-methyl-n-nitrosourea in Female Virgin Rats

Posted: 
March 6, 2017
Authors: 
Boshra SA, Hussein MA
Journal: 
Int J Phytomed 8(2):217-27
Abstract: 

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 and Cancer: An Update of Preclinical Studies Evaluating the Cancer Inhibitory Potential of Cranberry and Cranberry Derived Constituents

Posted: 
March 1, 2017
Authors: 
Weh KM, Clarke J, Kresty LA
Journal: 
Antioxidants 5(3):27
Abstract: 

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.

Cranberry Intervention in Patients with Prostate Cancer Prior to Radical Prostatectomy. Clinical, Pathological, and Laboratory Findings

Posted: 
March 1, 2017
Authors: 
Student V, Vidlar A, Bouchal J, Vrbkova J, Kolar Z, Kral M, Kosina P, Vostalova J
Journal: 
Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 160(4):559-565
Abstract: 

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.

Metabolism and Growth Inhibitory Activity of Cranberry Derived Flavonoids in Bladder Cancer Cells

Posted: 
March 1, 2017
Authors: 
Prasain JK, Rajbhandari R, Keeton AB, Piazza GA, Barnes S
Journal: 
Food Funct 7(9):4012-4019
Abstract: 

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.

Anti-leukopenic and antioxidant effects of cranberry extract in benzene and fluorouracil induced leukopenia in rats

Posted: 
August 22, 2016
Authors: 
Hussein M.A., Boshra S.A.
Journal: 
International Journal of Applied Research in Natural Products. 9 (1) (pp 1-8), 2016
Abstract: 

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.

Cranberry Proanthocyanidins Inhibit Esophageal Adenocarcinoma In Vitro and In Vivo Through Pleiotropic Cell Death Induction and PI3K/AKT/mTOR Inactivation.

Posted: 
March 23, 2016
Authors: 
Kresty LA, Weh KM, Zeyzus-Johns B, Perez LN, Howell AB
Journal: 
Oncotarget 6(32):33438-55
Abstract: 

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.

Cranberry extract suppresses interleukin-8 secretion from stomach cells stimulated by Helicobacter pylori in every clinically separated strain but inhibits growth in part of the strains.

Posted: 
February 15, 2014
Authors: 
Matsushima M, Suzuki T, Masui A, Mine T, Takagi A
Journal: 
J Funct Foods 5(2):729-735
Abstract: 

It is known that cranberry inhibits the growth of Helicobacter pylori (HP). In human stomach, HP basically induces chronic inflammation by stimulating stomach cells to secrete interleukin (IL)-8 and other inflammatory cytokines, and causes stomach cancer, etc. The aim of this study was to investigate the inhibiting effects of cranberry on HP growth and IL-8 secretion from stomach cells induced by HP, using clinically separated HP strains. HP growth in liquid culture and on-plate culture was evaluated by titration after 2-day incubation and by agar dilution technique, respectively. For IL-8 experiments, MKN-45, a stomach cancer cell line, was incubated with HP for 24 h and IL-8 in the medium was assayed by ELISA. Cranberry suppressed growth of the bacteria only in six of the 27 strains. Meanwhile, it suppressed IL-8 secretion in all the strains. The results may suggest a possible role of cranberry in prevention of stomach cancer by reducing gastric inflammation.

Cranberry extract suppresses interleukin-8 secretion from stomach cells stimulated by Helicobacter pylori in every clinically separated strain but inhibits growth in part of the strains

Posted: 
September 15, 2013
Authors: 
Matsushima M, Suzuki T, Masui A, Mine T, Takagi A
Journal: 
J Funct Food 5(2):729–35
Abstract: 

It is known that cranberry inhibits the growth of Helicobacter pylori (HP). In human stomach, HP basically induces chronic inflammation by stimulating stomach cells to secrete interleukin (IL)-8 and other inflammatory cytokines, and causes stomach cancer, etc. The aim of this study was to investigate the inhibiting effects of cranberry on HP growth and IL-8 secretion from stomach cells induced by HP, using clinically separated HP strains. HP growth in liquid culture and on-plate culture was evaluated by titration after 2-day incubation and by agar dilution technique, respectively. For IL-8 experiments, MKN-45, a stomach cancer cell line, was incubated with HP for 24 h and IL-8 in the medium was assayed by ELISA. Cranberry suppressed growth of the bacteria only in six of the 27 strains. Meanwhile, it suppressed IL-8 secretion in all the strains. The results may suggest a possible role of cranberry in prevention of stomach cancer by reducing gastric inflammation.

American cranberry (Vaccinium macrocarpon) extract affects human prostate cancer cell growth via cell cycle arrest by modulating expression of cell cycle regulators

Posted: 
April 30, 2012
Authors: 
Deziel B, MacPhee J, Patel K, Catalli A, Kulka M, Neto C,
Journal: 
Food Funct DOI: 10.1039/c2fo10145a
Abstract: 

Prostate cancer is one of the most common cancers in the world, and its prevalence is expected to increase appreciably in the coming decades. As such, more research is necessary to understand the etiology, progression and possible preventative measures to delay or to stop the development of this disease. Recently, there has been interest in examining the effects of whole extracts from commonly harvested crops on the behaviour and progression of cancer. Here, we describe the effects of whole cranberry extract (WCE) on the behaviour of DU145 human prostate cancer cells in vitro. Following treatment of DU145 human prostate cancer cells with 10, 25 and 50 mg ml 1 of WCE, respectively for 6 h, WCE significantly decreased the cellular viability of DU145 cells. WCE also decreased the
proportion of cells in the G2-M phase of the cell cycle and increased the proportion of cells in the G1 phase of the cell cycle following treatment of cells with 25 and 50 mg ml 1 treatment of WCE for 6 h. These alterations in cell cycle were associated with changes in cell cycle regulatory proteins and other cell cycle associated proteins. WCE decreased the expression of CDK4, cyclin A, cyclin B1, cyclin D1 and cyclin E, and increased the expression of p27. Changes in p16INK4a and pRBp107 protein expression
levels also were evident, however, the changes noted in p16INK4a and pRBp107 protein expression levels
were not statistically significant. These findings demonstrate that phytochemical extracts from the
American cranberry (Vaccinium macrocarpon) can affect the behaviour of human prostate cancer cells in vitro and further support the potential health benefits associated with cranberries.

Cancer chemopreventive effect of fractions from cranberry products

Posted: 
April 30, 2012
Authors: 
Caillet S, Lorenzo G, Côté J, Doyon G, Sylvain JF, Lacroix M
Journal: 
Food Res Int 45;320–330
Abstract: 

"Cancer chemopreventive properties were evaluated in HPLC fractions of different polarity obtained from two
cranberry juices and three extracts isolated from frozen cranberries and pomace containing anthocyanins,
water-soluble and apolar phenolic compounds, respectively. Compounds with close polarities were collected in order to obtain between three and four fractions from each juice or extract. Cranberry fractions were screened for their ability to induce the phase II xenobiotic detoxification enzyme quinone reductase (QR).
The results showed that there was no cytotoxicity against the cells used in the test. All samples stimulated
the quinone reductase activity except the highest concentrations of the less polar fraction of anthocyaninrich extract from pomace, which inhibited the QR activity. The QR induction for all samples varied with the concentration and there was an optimal concentration for which the QR induction was maximal. The technological process to manufacture cranberry juice had little influence on the overall QR inducer potencies of
cranberry fractions, whereas the ability of phenols in fractions to stimulate the QR activity has been reduced
significantly (P≤0.05) during the technological process. Among all samples, phenolic compounds of eight
fractions presented a maximum QR induction greater than 100 II(QR)/mg phenol. The phenolic compounds
of the most polar fraction (rich in phenolic acids) and those of the less polar fraction (rich in proanthocyanidins)
showed stronger induction than those observed with phenols from intermediate fractions."

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