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Oncology/Anti-Cancer

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Bioactive Components of Polyphenol-Rich and Non-Polyphenol-Rich Cranberry Fruit Extracts and Their Chemopreventive Effects on Colitis-Associated Colon Cancer

Posted: 
March 2, 2021
Authors: 
Wu X; Xue L; Tata A; Song M; Neto CC; Xiao H.
Journal: 
Journal of Agricultural & Food Chemistry. 68(25):6845-6853,
Abstract: 

Cranberries contain various constituents relevant to human health. Our previous study demonstrated the chemopreventive effects of whole cranberry against colon cancer in mice. In order to determine the role of different cranberry secondary metabolites in inhibiting colon cancer, cranberry ethyl acetate extract (EAE) and polyphenol extract (PPE) were obtained. The free-radical scavenging activities and chemical composition of the cranberry extracts were determined. EAE consisted of triterpenes and sterols and a trace amount of proanthocyanidins. PPE mainly contained polyphenol with a trace amount of triterpenes. The chemopreventive effects of orally administered EAE and PPE on colitis-associated colon carcinogenesis were determined in mice. Dietary EAE and PPE significantly suppressed tumor metrics without noticeable adverse effects. Gene expression levels of key proinflammatory cytokines were also attenuated by EAE and PPE in the mouse colon. In conclusion, the novel cranberry extracts may offer an efficacious and safe means to prevent colonic tumorigenesis in humans.

Cranberry anti-cancer compounds and their uptake and metabolism: an updated review

Posted: 
March 2, 2021
Authors: 
Prasain, J. K.; Grubbs, C.; Barnes, S..
Journal: 
Journal of Berry Research; 2020. 10(1):1-10.
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 extract initiates intrinsic apoptosis in HL-60 cells by increasing BAD activity through inhibition of AKT phosphorylation

Posted: 
March 2, 2021
Authors: 
Mansouri RA; Percival SS.
Journal: 
BMC Complementary Medicine and Therapies. 20(1):71,
Abstract: 

BACKGROUND: Cranberry has been studied as a potential anticancer agent as it is capable of inducing apoptosis within cancer cells. The aim of this study was to better define the mechanism by which cranberry triggers apoptosis in HL-60 cells. METHODS: The study was carried on cranberry extracts (CB). Anti-apoptotic B-cell lymphoma-2 (BCL-2) and pro-apoptotic BCL-2-associated death promoter death (BAD) proteins in cell lysates were detected through Western blotting techniques. Equivalent protein loading was confirmed through anti-alpha-tubulin antibody. RESULTS: The results showed that treatment of HL-60 cells with CB causes a significant increase in the levels of caspase-9 and caspases-3/7 and increased mitochondrial outer membrane permeability, leading to the release of cytochrome C and Smac. These apoptotic events were associated with a significant decrease in protein kinase B (AKT) phosphorylation, which caused significant increase in BAD de-phosphorylation and promoted a sequence of events that led to intrinsic apoptosis. CONCLUSION: The study findings have described a molecular framework for CB-initiated apoptosis in HL-60 cells and suggested a direction for future in vivo studies investigating the anticancer effect of cranberry

Potential of cranberry for suppressing Helicobacter pylori, a risk factor for gastric cancer.

Posted: 
March 2, 2021
Authors: 
Howell, A. B
Journal: 
Journal of Berry Research; 2020. 10(1):11-20.
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

The synergistic effect of cell wall extracted from probiotic biomass containing Lactobacillus acidophilus CL1285, L. casei LBC80R, and L. rhamnosus CLR2 on the anticancer activity of cranberry juice-HPLC fractions.

Posted: 
March 2, 2021
Authors: 
Desrouilleres, K.; Millette, M.; Bagheri, L.; Maherani, B.; Jamshidian, M.; Lacroix, M..
Journal: 
Journal of Food Biochemistry; 2020. 44(5).
Abstract: 

Anticancer effects were evaluated on three HPLC fractions obtained from a concentrated cranberry juice and cell wall constituents extracted from a probiotic biomass containing Lactobacillus acidophilus CL1285, Lactobacillus casei LBC80R, and Lactobacillus rhamnosus CLR2. The samples were tested at increasing concentrations for the antiproliferative assay using HT-29 cells' line and for the quinone reductase (QR) assay using Hepa-1c1c7 murine hepatoma cells. Fraction 1 (F1) which is highly concentrated with phenolic acids inhibited the growth of the HT-29 cells' line with IC50 values of 14.80 micro g Gallic acid equivalent (GAE)/ml. The fraction 3 (F3) which is highly concentrated in flavonols had potency as QR inducer. Furthermore, the results showed that all cranberry fractions combined with cell wall constituents extracted from the probiotic biomass were more effective in inhibiting the growth of HT-29 as compared to the cranberry fractions tested alone, indicating a possible synergy effect between these bio-functional compounds..

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.

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