A Brief Review of the Controversial Role of Iron in Colorectal Carcinogenesis

Cho, Margaret; Eze, Ogechukwu; Xu, Ruliang

doi:10.4172/2161-0681.1000137

Cited by 10 publications

(7 citation statements)

References 51 publications

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“…Now, the role of iron in human carcinogenesis remains under intensive discussion (Cho et al, 2013; Fonseca-Nunes et al, 2014). Here, I discuss the recent results from a genuine Fenton reaction-induced carcinogenesis model generated by intraperitoneal injections of an iron chelate, ferric nitrilotriacetate (Fe-NTA), to rodents (Ebina et al, 1986; Li et al, 1987).…”

Section: Iron As a Risk Of Cancermentioning

confidence: 99%

“…There are several review articles published on the direct demonstration of iron overload and carcinogenesis in animal experiments (Toyokuni, 1996 , 2002 , 2009 ; Beguin et al, 2014 ), which I summarize as Table 1 . Now, the role of iron in human carcinogenesis remains under intensive discussion (Cho et al, 2013 ; Fonseca-Nunes et al, 2014 ). Here, I discuss the recent results from a genuine Fenton reaction-induced carcinogenesis model generated by intraperitoneal injections of an iron chelate, ferric nitrilotriacetate (Fe-NTA), to rodents (Ebina et al, 1986 ; Li et al, 1987 ).…”

Section: Iron As a Risk Of Cancermentioning

confidence: 99%

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Iron and thiols as two major players in carcinogenesis: friends or foes?

Toyokuni

2014

Front. Pharmacol.

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Iron is the most abundant metal in the human body and mainly works as a cofactor for proteins such as hemoglobin and various enzymes. No independent life forms on earth can survive without iron. However, excess iron is intimately associated with carcinogenesis by increasing oxidative stress via its catalytic activity to generate hydroxyl radicals. Biomolecules with redox-active sulfhydryl function(s) (thiol compounds) are necessary for the maintenance of mildly reductive cellular environments to counteract oxidative stress, and for the execution of redox reactions for metabolism and detoxification. Involvement of glutathione S-transferase and thioredoxin has long attracted the attention of cancer researchers. Here, I update recent findings on the involvement of iron and thiol compounds during carcinogenesis and in cancer cells. It is now recognized that the cystine/glutamate transporter (antiporter) is intimately associated with ferroptosis, an iron-dependent, non-apoptotic form of cell death, observed in cancer cells, and also with cancer stem cells; the former with transporter blockage but the latter with its stabilization. Excess iron in the presence of oxygen appears the most common known mutagen. Ironically, the persistent activation of antioxidant systems via genetic alterations in Nrf2 and Keap1 also contributes to carcinogenesis. Therefore, it is difficult to conclude the role of iron and thiol compounds as friends or foes, which depends on the quantity/distribution and induction/flexibility, respectively. Avoiding further mutation would be the most helpful strategy for cancer prevention, and myriad of efforts are being made to sort out the weaknesses of cancer cells.

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Section: Iron As a Risk Of Cancermentioning

confidence: 99%

Section: Iron As a Risk Of Cancermentioning

confidence: 99%

Iron and thiols as two major players in carcinogenesis: friends or foes?

Toyokuni

2014

Front. Pharmacol.

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“…Although the reasons for the iron overload in our study remain largely unknown, the mechanism by which it could be related to CRA is known. Several studies have reported that iron overload mediated colonic tumorigenesis via increased ROS generation and inflammation [ 54 ]. One of the possible explanations is the synergistic effect of iron and non-amidated gastrins, including Gamide, progastrin and Ggly, which are peptide hormones regulating gastric acid secretion and gastric cell proliferation [ 54 ].…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have reported that iron overload mediated colonic tumorigenesis via increased ROS generation and inflammation [ 54 ]. One of the possible explanations is the synergistic effect of iron and non-amidated gastrins, including Gamide, progastrin and Ggly, which are peptide hormones regulating gastric acid secretion and gastric cell proliferation [ 54 ]. Non-amidated gastrins have been proposed to catalyze the loading of transferrin with iron [ 55 ].…”

Section: Discussionmentioning

confidence: 99%

Associations of Human Colorectal Adenoma with Serum Biomarkers of Body Iron Stores, Inflammation and Antioxidant Protein Thiols

et al. 2021

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Red and processed meat consumption and obesity are established risk factors for colorectal adenoma (CRA). Adverse changes in biomarkers of body iron stores (total serum iron, ferritin, transferrin and transferrin saturation), inflammation (high-sensitivity C-reactive protein [hs-CRP]) and anti-oxidative capacity (total of thiol groups (-S-H) of proteins [SHP]) might reflect underlying mechanisms that could explain the association of red/processed meat consumption and obesity with CRA. Overall, 100 CRA cases (including 71 advanced cases) and 100 CRA-free controls were frequency-matched on age and sex and were selected from a colonoscopy screening cohort. Odds ratios (OR) and 95% confidence intervals (95%CI) for comparisons of top and bottom biomarker tertiles were derived from multivariable logistic regression models. Ferritin levels were significantly positively associated with red/processed meat consumption and hs-CRP levels with obesity. SHP levels were significantly inversely associated with obesity. Transferrin saturation was strongly positively associated with overall and advanced CRA (ORs [95%CIs]: 3.05 [1.30–7.19] and 2.71 [1.03–7.13], respectively). Due to the high correlation with transferrin saturation, results for total serum iron concentration were similar (but not statistically significant). Furthermore, SHP concentration was significantly inversely associated with advanced CRA (OR [95%CI]: 0.29 [0.10–0.84]) but not with overall CRA (OR [95%CI]: 0.65 [0.27–1.56]). Ferritin, transferrin, and hs-CRP levels were not associated with CRA. Conclusions: High transferrin saturation as a sign of iron overload and a low SHP concentration as a sign of redox imbalance in obese patients might reflect underlying mechanisms that could in part explain the associations of iron overload and obesity with CRA.

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“…In addition to the elevated Zn level, an age-related increase and excess in Co and Fe mass fractions in prostatic tissue may contribute to the harmful effect on the gland. There are good reasons for such speculations about Fe since several reviews and many papers raise the concern about carcinogenicity of this metal overload (74)(75)(76)(77)(78). It was also shown that cobalt may be human carcinogen, but the experimental and epidemiologic data are limited (79)(80)(81).…”

Section: Discussionmentioning

confidence: 99%

Dietary Intake of Minerals and Prostate Cancer: Insights Into Problem Based on the Chemical Element Contents in the Prostate Gland

Zaichick¹,

Zaichick²

2015

J Aging Res & Lifestyle

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Objective: As men age total dietary mineral bioavailability falls which may increase the risk of prostate cancer. The aims of this study were to investigate the changes in main mineral contents in prostate gland that occurred with aging. Design: Population based study on changes in mineral contents in prostate gland with ageing. Participants and setting: 65 free-living healthy men aged 21-87 years who had died suddenly. Prostates were removed at necropsy and the samples of morphologic normal prostate tissue were investigated. Measurements: Contents of ten main minerals (B, Ca, Co, Cr, Cu, Fe, Mg, Mn, Se, and Zn) were determined by four instrumental analytical methods. Results: No any age-related deficiencies in minerals such as B, Ca, Co, Cr, Cu, Fe, Mg, Mn, Se, and Zn in the prostate tissue were found. Moreover, the mean mass fractions of Co, Fe, and Zn in prostate tissue for the age group adult men aged 41 years and older were statistically significant higher than for those younger than 40 years. Conclusions: Ageing is not associated with reduced mineral contents in prostate gland resulting in inadequate intakes in nutrients. Nutrition policy for men aged 41 years and older should include advice to decrease intakes of red meat for the purpose to reduce Fe and Zn intake.

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A Brief Review of the Controversial Role of Iron in Colorectal Carcinogenesis

Cited by 10 publications

References 51 publications

Iron and thiols as two major players in carcinogenesis: friends or foes?

Iron and thiols as two major players in carcinogenesis: friends or foes?

Associations of Human Colorectal Adenoma with Serum Biomarkers of Body Iron Stores, Inflammation and Antioxidant Protein Thiols

Dietary Intake of Minerals and Prostate Cancer: Insights Into Problem Based on the Chemical Element Contents in the Prostate Gland

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