Human and experimental colon carcinogenesis are enhanced by a pro-inflammatory microenvironment. Pharmacologically driven chemopreventive agents and dietary variables are hypothesized to have future roles in the prevention of colon cancer by targeting these processes. The current study was designed to determine the ability of dietary lyophilized strawberries to inhibit inflammation-promoted colon carcinogenesis in a preclinical animal model. Mice were given a single i.p. injection of azoxymethane (10 mg kg−1 body weight). One week after injection, mice were administered 2% (w/v) dextran sodium sulfate in drinking water for seven days and then an experimental diet containing chemically characterized lyophilized strawberries for the duration of the bioassay. Mice fed control diet, or experimental diet containing 2.5%, 5.0% or 10.0% strawberries displayed tumor incidence of 100%, 64%, 75% and 44%, respectively (p < 0.05). The mechanistic studies demonstrate that strawberries reduced expression of proinflammatory mediators, suppressed nitrosative stress and decreased phosphorylation of phosphatidylinositol 3-kinase, Akt, extracellular signal-regulated kinase and nuclear factor kappa B. In conclusion, strawberries target proinflammatory mediators and oncogenic signaling for the preventive efficacies against colon carcinogenesis in mice. This works supports future development of fully characterized and precisely controlled functional foods for testing in human clinical trials for this disease.
Colorectal cancer (CRC) is still a big health burden worldwide. Nutrition and dietary factors are known to affect colorectal cancer development and prognosis. The protective roles of diets rich in fruits and vegetables have been previously reported to contain high levels of cancer-fighting phytochemicals. Anthocyanins are the most abundant flavonoid compounds that are responsible for the bright colors of most blue, purple, and red fruits and vegetables, and have been shown to contribute to the protective effects of fruits and vegetables against cancer and other chronic diseases. Berries and grapes are the most common anthocyanin-rich fruits with antitumor effects. The antitumor effects of anthocyanins are determined by their structures and bioavailability as well as how they are metabolized. In this review, we aimed to discuss the preventive as well as therapeutic potentials of anthocyanins in CRC. We summarized the antitumor effects of anthocyanins and the mechanisms of action. We also discussed the potential pharmaceutical application of anthocyanins in practice.
Colorectal cancer (CRC) remains the third most common cause of cancer-related death in the United States and the fourth globally with a rising incidence. Inflammatory bowel disease (IBD) is a chronic immunologically mediated disease that imposes a significant associated health burden, including the increased risk for colonic dysplasia and CRC. Carcinogenesis has been attributed to chronic inflammation and associated with oxidative stress, genomic instability, and immune effectors as well as the cytokine dysregulation and activation of the nuclear factor kappa B (NFκB) signaling pathway. Current anti-inflammation therapies used for IBD treatment have shown limited effects on CRC chemoprevention, and their long-term toxicity has limited their clinical application. However, natural food-based prevention approaches may offer significant cancer prevention effects with very low toxicity profiles. In particular, in preclinical and clinical pilot studies, strawberry and black raspberry have been widely selected as food-based interventions because of their potent preventive activities. In this review, we summarize the roles of strawberry, black raspberry, and their polyphenol components on CRC chemoprevention in IBD.
Research in the laboratory has shown that lyophilized black raspberries (BRB) significantly inhibit N-nitrosomethylbenzylamine (NMBA)-induced esophageal squamous cell carcinogenesis in rats. The objective of the present study is to characterize the underlying mechanism(s) of anti-cancer action of BRB in this preclinical animal model focusing on oxidative stress and its related oncogenic signaling pathways. Esophageal epithelial tissues were collected and assessed for markers of oxidative stress and nuclear factor κB (NFκB) and mitogen-activated protein kinase (MAPK). BRB reduced the incidence of esophageal cancer from 100% in NMBA-treated rats to 81.5% in rats treated with NMBA plus BRB (p < 0.05). Tumor multiplicity was reduced from 4.73 ± 0.45 tumors per esophagus in NMBA-treated rats to 1.44 ± 0.26 in rats treated with NMBA plus BRB (p < 0.001). The data indicated that NMBA treatment increased production of hydrogen peroxide and lipid hydroperoxide, reduced expression and activity of glutathione peroxidase and superoxide dismutase 2, and activated NFκB/MAPK signaling in rat esophagus. The study’s results show that BRB reverses oxidative stress and suppresses NFκB/MAPK pathways, which could be the mechanisms for esophageal cancer chemopreventive action of BRB in rats.
We evaluated associations of the Empirical Dietary Index for Hyperinsulinemia (EDIH), Empirical Dietary Inflammatory Pattern (EDIP) and Healthy Eating Index (HEI2015) and their metabolomics profiles with the risk of total and site-specific cancers. We used baseline food frequency questionnaires to calculate dietary scores among 112,468 postmenopausal women in the Women’s Health Initiative. We used multivariable-adjusted Cox regression to estimate hazard ratios (HR) and 95% confidence intervals for cancer risk estimation. Metabolomic profile scores were derived using elastic-net regression with leave-one-out cross validation. In over 17.8 years, 18,768 incident invasive cancers were adjudicated. Higher EDIH and EDIP scores were associated with greater total cancer risk, and higher HEI-2015 with lower risk: HRQ5vsQ1(95% CI): EDIH, 1.10 (1.04–1.15); EDIP, 1.08 (1.02–1.15); HEI-2015, 0.93 (0.89–0.98). The multivariable-adjusted incidence rate difference(Q5vsQ1) for total cancer was: +52 (EDIH), +41 (EDIP) and −49 (HEI-2015) per 100,000 person years. All three indices were associated with colorectal cancer, and EDIH and EDIP with endometrial and breast cancer risk. EDIH was further associated with luminal-B, ER-negative and triple negative breast cancer subtypes. Dietary patterns contributing to hyperinsulinemia and inflammation were associated with greater cancer risk, and higher overall dietary quality, with lower risk. The findings warrant the testing of these dietary patterns in clinical trials for cancer prevention among postmenopausal women.