The role of antioxidants and pro-oxidants in colon cancer

Stone, William L.; Krishnan, Koyamangalath; Campbell, Sharon; Palau, Victoria

doi:10.4251/wjgo.v6.i3.55

Cited by 71 publications

(47 citation statements)

References 80 publications

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“…The results of a recent review of case–control and cohort studies on dietary patterns and CRC risk indicate that a plant-based pattern with moderate amounts of dairy, a pattern that is usually characterised by a high variety of vitamins and minerals, was associated with a lower CRC risk (Fung and Brown, 2013). Possible explanations for the apparent protective effect of PC2 may come from the antioxidant properties of nutrients with high loadings on PC2 including β -carotene and vitamin C that may reduce cell proliferation (World Cancer Research Fund/American Institute for Cancer Research, 2007; Stone et al , 2014). One of the most striking differences between PC1 and PC2 is the differential loading of vitamin B 12 .…”

Section: Discussionmentioning

confidence: 99%

Main nutrient patterns and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition study

et al. 2016

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Background:Much of the current literature on diet–colorectal cancer (CRC) associations focused on studies of single foods/nutrients, whereas less is known about nutrient patterns. We investigated the association between major nutrient patterns and CRC risk in participants of the European Prospective Investigation into Cancer and Nutrition (EPIC) study.Methods:Among 477 312 participants, intakes of 23 nutrients were estimated from validated dietary questionnaires. Using results from a previous principal component (PC) analysis, four major nutrient patterns were identified. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed for the association of each of the four patterns and CRC incidence using multivariate Cox proportional hazards models with adjustment for established CRC risk factors.Results:During an average of 11 years of follow-up, 4517 incident cases of CRC were documented. A nutrient pattern characterised by high intakes of vitamins and minerals was inversely associated with CRC (HR per 1 s.d.=0.94, 95% CI: 0.92–0.98) as was a pattern characterised by total protein, riboflavin, phosphorus and calcium (HR (1 s.d.)=0.96, 95% CI: 0.93–0.99). The remaining two patterns were not significantly associated with CRC risk.Conclusions:Analysing nutrient patterns may improve our understanding of how groups of nutrients relate to CRC.

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Section: Discussionmentioning

confidence: 99%

Main nutrient patterns and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition study

et al. 2016

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“…26 Viability of HCT 116 Colon Cancer Cell Line. Exposure to CeO 2 at different concentrations (5,10,20,40,60,80, and 100 μg/mL) led to cell death with a significantly lower IC 50 of 50.48 μg/mL, as compared to the relatively toxic anticancer drug. At a dose of 28.12 and 72.86 μg/mL, 30 and 70% of cell deaths were observed, respectively ( Figure 2).…”

Section: ■ Introductionmentioning

confidence: 99%

Pro-Oxidant Therapeutic Activities of Cerium Oxide Nanoparticles in Colorectal Carcinoma Cells

et al. 2020

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Given that basal levels of reactive oxygen species (ROS) are higher in cancer cells, there is a growing school of thought that endorses pro-oxidants as potential chemotherapeutic agents. Intriguingly, cerium oxide (CeO 2 ) nanoparticles can manifest either anti-or pro-oxidant activity as a function of differential pH of various subcellular localizations. In an acidic pH environment, for example, in extracellular milieu of cancer cells, CeO 2 would function as a pro-oxidant. Based on this concept, the present study is designed to investigate the pro-oxidant activities of CeO 2 in human colorectal carcinoma cell line (HCT 116). For comparison, we have also studied the effect of ceria nanoparticles on human embryonic kidney (HEK 293) cells. Dose-dependent viability of cancerous as well as normal cells has been assessed by treating them independently with CeO 2 nanoparticles of different concentrations (5−100 μg/mL) in the culture media. The half maximal inhibitory concentration (IC 50 ) of nanoceria for HCT 116 is found to be 50.48 μg/mL while that for the HEK 293 cell line is 92.03 μg/mL. To understand the intricate molecular mechanisms of CeO 2 -induced cellular apoptosis, a series of experiments have been conducted. The apoptosis-inducing ability of nanoceria has been investigated by Annexin V-FITC staining, caspase 3/9 analysis, cytochrome c release, intracellular ROS analysis, and mitochondrial membrane potential analysis using flow cytometry. Experimental data suggest that CeO 2 treatment causes DNA fragmentation through enhanced generation of ROS, which ultimately leads to cellular apoptosis through the p53-dependent mitochondrial signaling pathway.

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“…ROS‐induced senescence is a particularly compelling mechanism that may mediate the variance in CRC risk among people, in light of the evidence showing aging and diet, the two most prominent risk factors for CRC, can promote an oxidative state in the colon (Stone, Krishnan, Campbell, & Palau, ). Cellular senescence is an irreversible growth arrest that occurs in response to a variety of different stimuli, including oxidative stress, radiation, and oncogenic stress (Rodier & Campisi, ).…”

Section: Introductionmentioning

confidence: 99%

Senescence‐associated tissue microenvironment promotes colon cancer formation through the secretory factor GDF15

et al. 2019

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The risk of colorectal cancer (CRC) varies between people, and the cellular mechanisms mediating the differences in risk are largely unknown. Senescence has been implicated as a causative cellular mechanism for many diseases, including cancer, and may affect the risk for CRC. Senescent fibroblasts that accumulate in tissues secondary to aging and oxidative stress have been shown to promote cancer formation via a senescence‐associated secretory phenotype (SASP). In this study, we assessed the role of senescence and the SASP in CRC formation. Using primary human colon tissue, we found an accumulation of senescent fibroblasts in normal tissues from individuals with advanced adenomas or carcinomas in comparison with individuals with no polyps or CRC. In in vitro and ex vivo model systems, we induced senescence using oxidative stress in colon fibroblasts and demonstrated that the senescent fibroblasts secrete GDF15 as an essential SASP factor that promotes cell proliferation, migration, and invasion in colon adenoma and CRC cell lines as well as primary colon organoids via the MAPK and PI3K signaling pathways. In addition, we observed increased mRNA expression of GDF15 in primary normal colon tissue from people at increased risk for CRC in comparison with average risk individuals. These findings implicate the importance of a senescence‐associated tissue microenvironment and the secretory factor GDF15 in promoting CRC formation.

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The role of antioxidants and pro-oxidants in colon cancer

Cited by 71 publications

References 80 publications

Main nutrient patterns and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition study

Main nutrient patterns and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition study

Pro-Oxidant Therapeutic Activities of Cerium Oxide Nanoparticles in Colorectal Carcinoma Cells

Senescence‐associated tissue microenvironment promotes colon cancer formation through the secretory factor GDF15

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