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Oncology/Anti-Cancer

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Cranberry A-type Proanthocyanidins Selectively Target Acute Myeloid Leukemia Cells

Posted: 
March 20, 2020
Authors: 
Laura M. Bystrom , Daniel P. Bezerra , Hsiao-Ting Hsu , Hongliang Zong , Luis A. Lara-Martínez , Jeanne P. De Leon , Megan Emmanuel , David Méry , Sara Gardenghi , Duane Hassane , Catherine C. Neto , Susanna Cunningham-Rundles , Michael W. Becker , Stefan
Journal: 
Blood Adv (2019) 3 (21): 3261–3265. https://doi.org/10.1182/bloodadvances.2018026633
Abstract: 

Most elderly patients affected with acute myeloid leukemia (AML) will relapse and die of their disease even after achieving complete remission, thus emphasizing the urgent need for new therapeutic approaches with minimum toxicity to normal hematopoietic cells. Cranberry (Vaccinium spp.) extracts have exhibited anticancer and chemopreventive properties that have been mostly attributed to A-type proanthocyanidin (A-PAC) compounds. A-PACs, isolated from a commercially available cranberry extract, were evaluated for their effects on leukemia cell lines, primary AML samples, and normal CD34+ cord blood specimens. Our results indicated potent and specific antileukemia activity in vitro. In addition, the antileukemia activity of A-PACs extended to malignant progenitor and stem cell populations, sparing their normal counterparts. The antileukemia effects of A-PACs were also observed in vivo using patient derived xenografts. Surprisingly, we found that the mechanism of cell death was driven by activation of NF-κB. Overall, our data suggest that A-PACs could be used to improve treatments for AML by targeting leukemia stem cells through a potentially novel pathway.

Cranberry Anti-Cancer Compounds and their Uptake and Metabolism: An Updated Review

Posted: 
March 20, 2020
Authors: 
Prasain, Jeevan K.; Grubbs, Clinton; Barnes, Stephen
Journal: 
Journal of Berry Research, vol. Pre-press, no. Pre-press, pp. 1-10, 2019; DOI: 10.3233/JBR-180370
Abstract: 

Consumption of cranberry fruits or juice rich in polyphenols is associated with a wide range of potential health benefits. We and others have previously showed that cranberry juice concentrate and its phytochemicals, flavonols, anthocyanins and A-type proanthocyandins, may have potential to be chemopreventive agents. Although a number of cranberry constituents have been implicated in cancer prevention, our understanding about which metabolites are bio-available to reach target sites and thereby elicit cancer chemopreventive properties is still lacking. However, poor plasma bioavailability of cranberry constituents may be overcome by their potential interactions with gut microbiota by providing cancer prevention through induction of compositional and functional modifications of gut microbiota. Well-designed clinical trials evaluating metabolic and gut microbiome changes associated with cranberry consumption would provide useful information about the cancer patient’s response to dietary intervention with cranberry constituents.

Cranberry as a Promising Natural Source of Potential Nutraceuticals with Anticancer Activity.

Posted: 
March 20, 2020
Authors: 
Mantzorou M; Zarros A; Theocharis S; Pavlidou E; Giaginis C.
Journal: 
Anticancer Agents Med Chem 10.2174/1871520619666190704163301 [doi]
Abstract: 

Studies have shown that cranberry and its components may exert anticancer properties. The present study aims to critically summarise the existing experimental studies evaluating the potential effects of cranberry on cancer prevention and treatment. PubMed database was searched to identify rele-vant studies. Current in vitro studies have indicated that cranberry and/or its components may act as chemopreventive agents, diminishing the risk for cancer by inhibiting cells oxidation and inflammatory-related processes, while they may also exert chemotherapeutic effects by inhibiting cell proliferation and angiogenesis, inducing cell apoptosis and attenuating the ability of tumour cells to invade and metastasis. Limited in vivo studies have further documented potential anticancer activity. Cranberry could be considered as a conglomeration of potential effective anticancer drug-like compounds.

Potential of Cranberry for Suppressing Helicobacter Pylori, A Risk Factor for Gastric Cancer

Posted: 
March 20, 2020
Authors: 
Howell, Amy B.
Journal: 
Journal of Berry Research, DOI: 10.3233/JBR-180375
Abstract: 

This review summarizes the mechanistic and clinical research on the use of cranberry as an alternative management strategy for H. pylori bacteria in populations at high risk for infection-induced peptic ulcers and gastric cancer. The multiple mechanisms of action of cranberry polyphenols and how they may be applied in relation to what is known about the pathogenicity of H. pylori offers opportunity for utilizing this fruit to potentially help lower the incidence of ulcers and concomitant gastric cancer.

Biotransformation of Cranberry Proanthocyanidins to Probiotic Metabolites by Lactobacillus rhamnosus Enhances Their Anticancer Activity in HepG2 Cells In Vitro.

Posted: 
August 29, 2019
Authors: 
Rupasinghe HPV; Parmar I; Neir SV.
Journal: 
Oxidative medicine & cellular longevity. 2019:4750795
Abstract: 

This study was designed to unravel the role of Lactobacillus rhamnosus in the bioconversion of cranberry proanthocyanidins and cytotoxicity of resulting metabolites to hepatocellular carcinoma HepG2 cells. Crude (CR) and flavonol+dihydrochalcone- (FL+DHC-), anthocyanin- (AN-), proanthocyanidin- (PR-), and phenolic acid+catechin- (PA+C-) rich fractions were subjected to fermentation with L. rhamnosus at 37degreeC for 12, 24, and 48 h under anaerobic conditions. The major metabolites produced by bioconversion of polyphenols were 4-hydroxyphenylacetic acid, 3-(4-hydroxyphenyl)propionic acid, hydrocinnamic acid, catechol, and pyrogallol. Furthermore, cytotoxicity of the biotransformed extracts was compared to their parent extracts using human hepatocellular carcinoma HepG2 cells. The results showed that PR-biotransformed extract completely inhibited HepG2 cell proliferation in a dose- and time-dependent manner with IC50 values of 47.8 and 20.1 mug/mL at 24 and 48 h, respectively. An insight into the molecular mechanisms involved revealed that the cytotoxic effects of PR at 24 h incubation were mitochondria-controlled and not by proapoptotic caspase-3/7 dependent. The present findings suggest that the application of a bioconversion process using probiotic bacteria can enhance the pharmacological activities of cranberry proanthocyanidins by generating additional biologically active metabolites.

Constitutively Higher Level of GSTT2 in Esophageal Tissues From African Americans Protects Cells Against DNA Damage.

Posted: 
August 29, 2019
Authors: 
Ferrer-Torres D; Nancarrow DJ; Steinberg H; Wang Z; Kuick R; Weh KM; Mills RE; Ray D; Ray P; Lin J; Chang AC; Reddy RM; Orringer MB; Canto MI; Shaheen NJ; Kresty LA; Chak A; Wang TD; Rubenstein JH; Beer DG.
Journal: 
Gastroenterology. 156(5):1404-1415
Abstract: 

BACKGROUND & AIMS: African American and European American individuals have a similar prevalence of gastroesophageal reflux disease (GERD), yet esophageal adenocarcinoma (EAC) disproportionately affects European American individuals. We investigated whether the esophageal squamous mucosa of African American individuals has features that protect against GERD-induced damage, compared with European American individuals. METHODS: We performed transcriptional profile analysis of esophageal squamous mucosa tissues from 20 African American and 20 European American individuals (24 with no disease and 16 with Barrett's esophagus and/or EAC). We confirmed our findings in a cohort of 56 patients and analyzed DNA samples from patients to identify associated variants. Observations were validated using matched genomic sequence and expression data from lymphoblasts from the 1000 Genomes Project. A panel of esophageal samples from African American and European American subjects was used to confirm allele-related differences in protein levels. The esophageal squamous-derived cell line Het-1A and a rat esophagogastroduodenal anastomosis model for reflux-generated esophageal damage were used to investigate the effects of the DNA-damaging agent cumene-hydroperoxide (cum-OOH) and a chemopreventive cranberry proanthocyanidin (C-PAC) extract, respectively, on levels of protein and messenger RNA (mRNA).RESULTS: We found significantly higher levels of glutathione S-transferase theta 2 (GSTT2) mRNA in squamous mucosa from African American compared with European American individuals and associated these with variants within the GSTT2 locus in African American individuals. We confirmed that 2 previously identified genomic variants at the GSTT2 locus, a 37-kb deletion and a 17-bp promoter duplication, reduce expression of GSTT2 in tissues from European American individuals. The nonduplicated 17-bp promoter was more common in tissue samples from populations of African descendant. GSTT2 protected Het-1A esophageal squamous cells from cum-OOH-induced DNA damage. Addition of C-PAC increased GSTT2 expression in Het-1A cells incubated with cum-OOH and in rats with reflux-induced esophageal damage. C-PAC also reduced levels of DNA damage in reflux-exposed rat esophagi, as observed by reduced levels of phospho-H2A histone family member X.CONCLUSIONS: We found GSTT2 to protect esophageal squamous cells against DNA damage from genotoxic stress and that GSTT2 expression can be induced by C-PAC. Increased levels of GSTT2 in esophageal tissues of African American individuals might protect them from GERD-induced damage and contribute to the low incidence of EAC in this population.

Chemopreventive Effects of Whole Cranberry (Vaccinium macrocarpon) on Colitis-Associated Colon Tumorigenesis.

Posted: 
February 19, 2019
Authors: 
Wu X, Song M, Cai X, Neto C, Tata A, Han Y, Wang Q, Tang Z, Xiao H.
Journal: 
Mol Nutr Food Res. 2018 Dec;62(24):e1800942. doi: 10.1002/mnfr.201800942.
Abstract: 

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.

Anticancer Activity of Chlorhexidine and Cranberry Extract: an In-Vitro Study.

Posted: 
September 4, 2018
Authors: 
Khairnar MR; Wadgave U; Jadhav H; Naik R.
Journal: 
Journal of Experimental Therapeutics & Oncology. 12(3):201-205
Abstract: 

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.

Dietary Feeding of Freeze-Dried Whole Cranberry Inhibits Intestinal Tumor Development in Apcmin/+ Mice.

Posted: 
April 4, 2018
Authors: 
Jin D; Liu T; Dong W; Zhang Y; Wang S; Xie R; Wang B; Cao H.
Journal: 
Oncotarget. 8(58):97787-97800
Abstract: 

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.

Evidence of Some Natural Products with Antigenotoxic Effects. Part 1: Fruits and Polysaccharides

Posted: 
August 15, 2017
Authors: 
Evidence of Some Natural Products with Antigenotoxic Effects. Part 1: Fruits and Polysaccharides
Journal: 
Nutrients 9(2)
Abstract: 

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.

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