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13 pages, 2196 KiB

Open AccessArticle

Dietary Inflammatory Index and Odds of Colorectal Cancer and Colorectal Adenomatous Polyps in a Case-Control Study from Iran

by Pegah Rafiee, Nitin Shivappa, James R. Hébert, Saeede Jaafari Nasab, Alireza Bahrami, Azita Hekmatdoost, Bahram Rashidkhani, Amir Sadeghi, Mohammad Houshyari and Ehsan Hejazi

Nutrients 2019, 11(6), 1213; https://doi.org/10.3390/nu11061213 - 28 May 2019

Cited by 21 | Viewed by 5171

Abstract

Background: Chronic inflammation is implicated in the development of colorectal cancer (CRC) and its precursor; colorectal adenomatous polyps (CAP). Some dietary factors are important triggers for systemic inflammation. Therefore, the present study aimed to investigate the association between the dietary inflammatory index (DII [...] Read more.

Background: Chronic inflammation is implicated in the development of colorectal cancer (CRC) and its precursor; colorectal adenomatous polyps (CAP). Some dietary factors are important triggers for systemic inflammation. Therefore, the present study aimed to investigate the association between the dietary inflammatory index (DII^®) and the risk of CRC and CAP in an Iranian case-control study. Methods: 134 newly diagnosed CRC patients, 130 newly diagnosed CAP patients, and 240 hospitalized controls were recruited using convenience sampling. Energy-adjusted DII (E-DII) scores were computed based on dietary intake assessed using a reproducible and valid 148-item food frequency questionnaire. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CI) after adjusting for confounders. Results: The E-DII score ranged between −4.23 (the most anti-inflammatory score) to +3.89 (the most pro-inflammatory score). The multivariable-adjusted ORs for participants in the 3rd tertile compared to the 1st tertile was 5.08 (95%CI: 2.70–9.56; P-trend < 0.0001) for CRC and 2.33 (95% CI: 1.30–4.02; P-trend = 0.005) for CAP. Conclusions: Our findings suggest that more pro-inflammatory diets, indicated by higher E-DII scores, might increase the risk of both CRC and CAP. Future steps should include testing these associations in a prospective setting in Iran. Full article

(This article belongs to the Special Issue Nutrition and Colorectal Cancer)

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20 pages, 2713 KiB

Open AccessFeature PaperArticle

Polymethoxylated Flavones Target Cancer Stemness and Improve the Antiproliferative Effect of 5-Fluorouracil in a 3D Cell Model of Colorectal Cancer

by Carolina V. Pereira, Marlene Duarte, Patrícia Silva, Andreia Bento da Silva, Catarina M. M. Duarte, Alejandro Cifuentes, Virginia García-Cañas, Maria R. Bronze, Cristina Albuquerque and Ana Teresa Serra

Nutrients 2019, 11(2), 326; https://doi.org/10.3390/nu11020326 - 02 Feb 2019

Cited by 31 | Viewed by 4927

Abstract

Polymethoxylated flavones (PMFs) from citrus fruits are reported to present anticancer potential. However, there is a lack of information regarding their effect on cancer stem cell (CSC) populations, which has been recognized as responsible for tumor initiation, relapse, and chemoresistance. In this study, [...] Read more.

Polymethoxylated flavones (PMFs) from citrus fruits are reported to present anticancer potential. However, there is a lack of information regarding their effect on cancer stem cell (CSC) populations, which has been recognized as responsible for tumor initiation, relapse, and chemoresistance. In this study, we evaluated the effect of an orange peel extract (OPE) and its main PMFs, namely, nobiletin, sinensetin, tangeretin, and scutellarein tetramethylether in targeting cell proliferation and stemness using a 3D cell model of colorectal cancer composed of HT29 cell spheroids cultured for 7 days in stirred conditions. Soft agar assay, ALDH1 activity, and relative quantitative gene expression analysis of specific biomarkers were carried out to characterize the stemness, self-renewal, and mesenchymal features of HT29 cell spheroids. Then, the impact of OPE and PMFs in reducing cell proliferation and modulating cancer stemness and self-renewal was assessed. Results showed that, when compared with monolayer cultures, HT29 cell spheroids presented higher ALDH1 activity (81.97% ± 5.27% compared to 63.55% ± 17.49% for 2D), upregulation of CD44, PROM1, SOX9, and SNAI1 genes (1.83 ± 0.34, 2.54 ± 0.51, 2.03 ± 0.15, and 6.12 ± 1.59 times) and high self-renewal capability (352 ± 55 colonies compared to 253 ± 42 for 2D). Incubation with OPE (1 mg/mL) significantly inhibited cell proliferation and modulated cancer stemness and self-renewal ability: colony formation, ALDH1 activity, and the expression of cancer stemness biomarkers PROM1 and LGR5 were significantly reduced (0.66 ± 0.15 and 0.51 ± 0.14 times, respectively). Among all PMFs, tangeretin was the most efficient in targeting the CSC population by decreasing colony formation and the expression of PROM1 and LGR5. Scutellarein tetramethylether was shown to modulate markers of mesenchymal/metastatic transition (increasing CDH1 and reducing ZEB1 and SNAI1) and nobiletin was capable of downregulating PROM1 and SNAI1 expression. Importantly, all PMFs and OPE were shown to synergistically interact with 5-fluorouracil, improving the antiproliferative response of this drug. Full article

(This article belongs to the Special Issue Nutrition and Colorectal Cancer)

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14 pages, 2112 KiB

Open AccessArticle

n-6 Linoleic Acid Induces Epigenetics Alterations Associated with Colonic Inflammation and Cancer

by Donato F. Romagnolo, Micah G. Donovan, Tom C. Doetschman and Ornella I. Selmin

Nutrients 2019, 11(1), 171; https://doi.org/10.3390/nu11010171 - 15 Jan 2019

Cited by 34 | Viewed by 5983

Abstract

The farnesoid-X-receptor (FXR) protects against inflammation and cancer of the colon through maintenance of intestinal bile acid (BA) homeostasis. Conversely, higher levels of BA and cyclooxygenase-2 (COX-2) are risk factors for inflammation and cancer of the colon. In the United States, n-6 [...] Read more.

The farnesoid-X-receptor (FXR) protects against inflammation and cancer of the colon through maintenance of intestinal bile acid (BA) homeostasis. Conversely, higher levels of BA and cyclooxygenase-2 (COX-2) are risk factors for inflammation and cancer of the colon. In the United States, n-6 linoleic acid (LA) is the most commonly used dietary vegetable fat. Metabolism of n-6 fatty acids has been linked to a higher risk of intestinal cancer. The objectives of this study were to investigate in colonic mucosa the effects of a high-fat diet rich in LA (n-6HFD) on CpG methylation of Fxr and prostaglandin-endoperoxide synthase-2 (Ptsg-2) genes, and the impact on the expression of tumor suppressor adenomatous polyposis Coli (Apc) and proliferative cyclin D1 (Ccnd1) genes. Weaned C57BL/6J male mice were fed for 6 weeks either an n-6HFD containing 44% energy (44%E) from 22% safflower oil (SO, 76% LA by weight) or a 13% energy (13%E) control diet (Control) from SO (5% by weight). Mice fed the n-6HFD had reduced (60%) Fxr promoter CpG methylation and increased (~50%) Fxr mRNA. The expression of FXR-target ileal bile acid-binding protein (Ibabp), small heterodimer protein (Shp), and anti-inflammatory peroxisome proliferator-activated-γ1 genes was increased. The n-6HFD reduced Ptgs-2 CpG methylation, increased the expression of Cox-2, and increased Apc CpG methylation in colonic mucosa. Accordingly, reduced expression of Apc was coupled to accumulation of c-JUN and Ccnd1, respectively cofactor and gene targets for the β-catenin/Wnt signaling pathway. Finally, the n-6HFD reduced the expression of histone deacetylase-1 while favoring the accumulation of acetylated histone 3. We conclude that an n-6HFD epigenetically modifies Fxr, leading to the activation of downstream factors that participate in BA homeostasis. However, epigenetic activation of Ptsg-2 coupled with silencing of Apc and accumulation of C-JUN and Ccnd1 may increase the risk of inflammation and cancer of the colon. Full article

(This article belongs to the Special Issue Nutrition and Colorectal Cancer)

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19 pages, 8834 KiB

Open AccessArticle

Tributyrin in Inflammation: Does White Adipose Tissue Affect Colorectal Cancer?

by Luana Amorim Biondo, Alexandre Abilio S. Teixeira, Loreana S. Silveira, Camila O. Souza, Raquel G. F. Costa, Tiego A. Diniz, Francielle C. Mosele and José Cesar Rosa Neto

Nutrients 2019, 11(1), 110; https://doi.org/10.3390/nu11010110 - 08 Jan 2019

Cited by 7 | Viewed by 6823

Abstract

Colorectal cancer affects the large intestine, leading to loss of white adipose tissue (WAT) and alterations in adipokine secretion. Lower incidence of colorectal cancer is associated with increased fibre intake. Fructooligosaccharides (FOS) are fibres that increase production of butyrate by the intestinal microbiota. [...] Read more.

Colorectal cancer affects the large intestine, leading to loss of white adipose tissue (WAT) and alterations in adipokine secretion. Lower incidence of colorectal cancer is associated with increased fibre intake. Fructooligosaccharides (FOS) are fibres that increase production of butyrate by the intestinal microbiota. Tributyrin, a prodrug of butyric acid, exerts beneficial anti-inflammatory effects on colorectal cancer. Our aim was to characterise the effects of diets rich in FOS and tributyrin within the context of a colon carcinogenesis model, and characterise possible support of tumorigenesis by WAT. C57/BL6 male mice were divided into four groups: a control group (CT) fed with chow diet and three colon carcinogenesis-induced groups fed either with chow diet (CA), tributyrin-supplemented diet (BUT), or with FOS-supplemented diet. Colon carcinogenesis decreased adipose mass in subcutaneous, epididymal, and retroperitoneal tissues, while also reducing serum glucose and leptin concentrations. However, it did not alter the concentrations of adiponectin, interleukin (IL)-6, IL-10, and tumour necrosis factor alpha (TNF)-α in WAT. Additionally, the supplements did not revert the colon cancer affected parameters. The BUT group exhibited even higher glucose tolerance and levels of IL-6, VEGF, and TNF-α in WAT. To conclude our study, FOS and butyrate supplements were not beneficial. In addition, butyrate worsened adipose tissue inflammation. Full article

(This article belongs to the Special Issue Nutrition and Colorectal Cancer)

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14 pages, 3648 KiB

Open AccessArticle

Cordyceps militaris Grown on Germinated Soybean Suppresses KRAS-Driven Colorectal Cancer by Inhibiting the RAS/ERK Pathway

by HeeJung Seo, Jisu Song, Minyoung Kim, Dong-Wook Han, Hye-Jin Park and Minjung Song

Nutrients 2019, 11(1), 20; https://doi.org/10.3390/nu11010020 - 21 Dec 2018

Cited by 11 | Viewed by 6737

Abstract

Cordyceps militaris is a commonly used medicinal mushroom containing various therapeutic effects such as anti-inflammatory, anti-allergic, and anti-cancer activities. This study examined whether Cordyceps militaris on germinated soybeans (GSC) has a suppressive effect on a v-ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS)-driven [...] Read more.

Cordyceps militaris is a commonly used medicinal mushroom containing various therapeutic effects such as anti-inflammatory, anti-allergic, and anti-cancer activities. This study examined whether Cordyceps militaris on germinated soybeans (GSC) has a suppressive effect on a v-ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS)-driven colorectal cancer which is notorious for its un-druggable features and the ineffectiveness of conventional therapies against it. GSC extract was prepared and its proximate composition and amino acids were analyzed. The suppressive effects were investigated with the KRAS-driven colorectal cancer cell-line, SW480. SW480 proliferation, clonogenic potential, apoptosis, and the RAS/extracellular signal-regulated kinase (ERK) pathway under the GSC treatment were analyzed by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay, flow cytometry, and Western blot, respectively. An in vivo experiment with the SW480 xenograft mouse model was performed. As a result, GSC suppressed cell proliferation by inducing the apoptosis of KRAS-driven colorectal cancer cells and inhibited clonogenic capabilities. The decrease of KRAS and ERK phosphorylation was detected by Western blot. Tumor growth was significantly suppressed when GSC was introduced to the tumor-xenograft mouse model. In conclusion, GSC suppressed KRAS-driven colorectal cancer growth both in vitro and in vivo, and can be used as an alternative or simultaneous approach in colorectal cancer therapy. Full article

(This article belongs to the Special Issue Nutrition and Colorectal Cancer)

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14 pages, 1235 KiB

Open AccessArticle

Dose-Response Relationship between Serum Retinol Levels and Survival in Patients with Colorectal Cancer: Results from the DACHS Study

by Haifa Maalmi, Viola Walter, Lina Jansen, Robert W. Owen, Alexis Ulrich, Ben Schöttker, Jenny Chang-Claude, Michael Hoffmeister and Hermann Brenner

Nutrients 2018, 10(4), 510; https://doi.org/10.3390/nu10040510 - 19 Apr 2018

Cited by 4 | Viewed by 4922

Abstract

Current knowledge on the role of retinol in the prognosis of patients with colorectal cancer (CRC) is very limited. We investigated the association of serum retinol levels with survival outcomes in a large cohort of 2908 CRC patients from Germany. Retinol concentrations were [...] Read more.

Current knowledge on the role of retinol in the prognosis of patients with colorectal cancer (CRC) is very limited. We investigated the association of serum retinol levels with survival outcomes in a large cohort of 2908 CRC patients from Germany. Retinol concentrations were determined in serum collected shortly after diagnosis by mass spectrometry. Associations between serum retinol levels and survival outcomes were assessed using multivariable Cox regression and dose-response analyses. The joint association of serum retinol and serum 25-hydroxyvitamin D₃ (25(OH)D₃) with survival outcomes was also examined. During a median follow-up of 4.8 years, 787 deaths occurred, 573 of which were due to CRC. Dose-response curves showed an inverse relationship between serum retinol levels and survival endpoints in the range of <2.4 µmol/L, but no associations at higher levels. Low (<1.2 µmol/L) versus high (≥2.4 µmol/L) serum retinol levels were associated with poorer overall survival (Hazard ratio (HR) = 1.46, 95% confidence interval (CI) = 1.19–1.78, P-trend = 0.0003) and CRC-specific survival (HR = 1.69, 95% CI = 1.33–2.15, P-trend < 0.0001). Joint presence of low serum retinol (<1.2 µmol/L) and low 25(OH)D₃ (<30 nmol/L) was associated with a particularly strong decrease in overall and CRC-specific survival. Low serum retinol levels were identified as a predictor of poor survival in CRC patients, in particular when co-occurring with low serum concentrations of 25(OH)D₃. The clinical implications of these findings require further investigation. Full article

(This article belongs to the Special Issue Nutrition and Colorectal Cancer)

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Review

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11 pages, 212 KiB

Open AccessReview

Colorectal Cancer and Nutrition

by Kannan Thanikachalam and Gazala Khan

Nutrients 2019, 11(1), 164; https://doi.org/10.3390/nu11010164 - 14 Jan 2019

Cited by 410 | Viewed by 43407

Abstract

Colorectal Cancer is the third most common cancer diagnosed in the US. While the incidence and the mortality rate of colorectal cancer has decreased due to effective cancer screening measures, there has been an increase in number of young patients diagnosed in colon [...] Read more.

Colorectal Cancer is the third most common cancer diagnosed in the US. While the incidence and the mortality rate of colorectal cancer has decreased due to effective cancer screening measures, there has been an increase in number of young patients diagnosed in colon cancer due to unclear reasons at this point of time. While environmental and genetic factors play a major role in the pathogenesis of colon cancer, extensive research has suggested that nutrition may play both a causal and protective role in the development of colon cancer. In this review article, we aim to provide a review of factors that play a major role in development of colorectal cancer. Full article

(This article belongs to the Special Issue Nutrition and Colorectal Cancer)

16 pages, 1985 KiB

Open AccessReview

Olive Oil Effects on Colorectal Cancer

by Antonio Maria Borzì, Antonio Biondi, Francesco Basile, Salvatore Luca, Enzo Saretto Dante Vicari and Marco Vacante

Nutrients 2019, 11(1), 32; https://doi.org/10.3390/nu11010032 - 23 Dec 2018

Cited by 74 | Viewed by 12782

Abstract

Colorectal cancer is the fourth cause of cancer-related death worldwide. A Mediterranean diet showed protective action against colorectal cancer due to the intake of different substances. Olive oil is a fundamental component of the Mediterranean diet. Olive oil is rich in high-value health [...] Read more.

Colorectal cancer is the fourth cause of cancer-related death worldwide. A Mediterranean diet showed protective action against colorectal cancer due to the intake of different substances. Olive oil is a fundamental component of the Mediterranean diet. Olive oil is rich in high-value health compounds (such as monounsaturated free fatty acids, squalene, phytosterols, and phenols). Phenolic compounds exert favourable effects on free radicals, inflammation, gut microbiota, and carcinogenesis. The interaction between gut microbiota and olive oil consumption could modulate colonic microbial composition or activity, with a possible role in cancer prevention. Gut microbiota is able to degrade some substances found in olive oil, producing active metabolites with chemopreventive action. Further clinical research is needed to clarify the beneficial effects of olive oil and its components. A better knowledge of the compounds found in olive oil could lead to the development of nutritional supplements or chemotherapeutic agents with a potential in the prevention and treatment of colorectal cancer. Full article

(This article belongs to the Special Issue Nutrition and Colorectal Cancer)

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