Iron: Key player in cancer and cell cycle?

Khan, Azmi; Singh, Pratika; Srivastava, Amrita

doi:10.1016/j.jtemb.2020.126582

Cited by 28 publications

(18 citation statements)

References 95 publications

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“…Consistent with other preclinical reports, effects were modest and not statistically significant [ 47 ]. More importantly, the data were consistent with three population studies published between 2019 and 2021 [ 6 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ]. Specifically, we evaluated the data ( Table 5 ) in a manner that paralleled the common approach in epidemiology, contrasting low versus high iron status, i.e., by comparing groups 1–3 vs. 4–7: the cancer incidence was 63.3 vs. 70.0 (RR = 1.10 (0.95, 1.20; p = 0.098)).…”

Section: Resultssupporting

confidence: 88%

“…Recently reported results from population studies, systematic reviews, and meta-analyses revealed no relationship between iron status and breast cancer, a weak positive association, or a small protective effect of low iron status [ 6 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ]. However, in most of those studies, the authors concluded that further investigation was merited.…”

Section: Resultsmentioning

confidence: 99%

“…The prevailing issues underlying those investigations included the impact of iron deficiency in limiting processes related to tumor development and the effects of excess iron-induced oxidative stress on the carcinogenic process. Papers published between 2017 and 2021 [ 6 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ] indicated that this cycle of interest is once again repeating. The prevailing hypotheses include not only those that were prominent in the 2008–2013 timeframe but also those that are centered on iron metabolism as regulated by hepcidin, with extension to how the gut microbiome and immune system might be involved in effect mediation.…”

Section: Introductionmentioning

confidence: 99%

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Pre-Clinical Insights into the Iron and Breast Cancer Hypothesis

2021

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Population studies, systematic reviews, and meta-analyses have revealed no relationship between iron status and breast cancer, a weak positive association, or a small protective effect of low iron status. However, in those studies, the authors concluded that further investigation was merited. The set of experiments reported here used preclinical models to assess the likely value of further investigation. The effects of iron status on the initiation and promotion stage of mammary carcinogenesis are reported. Using the classical model of cancer initiation in the mammary gland, 7,12 dimethyl-benz[α]anthracene-induced carcinogenesis was unaffected by iron status. Similarly, excess iron intake showed no effect on the promotion stage of 1-methyl-1-nitrosurea-induced mammary carcinogenesis, though iron deficiency exerted a specific inhibitory effect on the carcinogenic process. Though iron-mediated cellular oxidation is frequently cited as a potential mechanism for effects on breast cancer, no evidence of increased oxidative damage to DNA attributable to excess iron intake was found. The reported preclinical data fail to provide convincing evidence that the further evaluation of the iron–breast cancer risk hypotheses is warranted and underscore the value of redefining the referent group in population-based studies of iron–cancer hypotheses in other tissues.

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Section: Resultssupporting

confidence: 88%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Pre-Clinical Insights into the Iron and Breast Cancer Hypothesis

2021

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“…PCNA and cyclin D1 have been suggested as hub genes related to CRC development and are powerful therapeutic targets reported to be upregulated in CRC [ 81 ]. Previously, iron depletion was reported to induce cell cycle arrest by reducing cyclin D1 levels in mantle cell lymphoma cells [ 82 ] and by reducing PCNA and cyclin D1 levels in a dose-dependent manner in immortalized Kaposi’s sarcoma cells [ 83 ]. Although chronic iron overload is known to increase cell proliferation [ 84 , 85 ], excessive iron can lead to increased ROS [ 86 ] and increased ROS can lead to lipid peroxidation, leading to ferroptosis [ 87 ].…”

Section: Discussionmentioning

confidence: 99%

Supplementation with High or Low Iron Reduces Colitis Severity in an AOM/DSS Mouse Model

Moon

Kim

et al. 2022

Nutrients

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The relationship between colitis-associated colorectal cancer (CAC) and the dysregulation of iron metabolism has been implicated. However, studies on the influence of dietary iron deficiency on the incidence of CAC are limited. This study investigated the effects of dietary iron deficiency and dietary non-heme iron on CAC development in an azoxymethane/dextran sodium sulfate (AOM/DSS) mouse model. The four-week-old mice were divided into the following groups: iron control (IC; 35 ppm iron/kg) + normal (NOR), IC + AOM/DSS, iron deficient (ID; <5 ppm iron/kg diet) + AOM/DSS, and iron overload (IOL; approximately 2000 ppm iron/kg) + AOM/DSS. The mice were fed the respective diets for 13 weeks, and the AOM/DSS model was established at week five. FTH1 expression increased in the mice’s colons in the IC + AOM/DSS group compared with that observed in the ID and IOL + AOM/DSS groups. The reduced number of colonic tumors in the ID + AOM/DSS and IOL + AOM/DSS groups was accompanied by the downregulated expression of cell proliferation regulators (PCNA, cyclin D1, and c-Myc). Iron overload inhibited the increase in the expression of NF-κB and its downstream inflammatory cytokines (IL-6, TNFα, iNOS, COX2, and IL-1β), likely due to the elevated expression of antioxidant genes (SOD1, TXN, GPX1, GPX4, CAT, HMOX1, and NQO1). ID + AOM/DSS may hinder tumor development in the AOM/DSS model by inhibiting the PI3K/AKT pathway by increasing the expression of Ndrg1. Our study suggests that ID and IOL diets suppress AOM/DSS-induced tumors and that long-term iron deficiency or overload may negate CAC progression.

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“…3,4 In addition, excess metal ions such as iron, copper, lead, cadmium and other metal ions in the human body will destroy bones and kidneys, cause hypertension, nervous system diseases and brain diseases. [5][6][7] For the detection of heavy metal ions, mass spectrometry, 8,9 electrochemical detection 10 and X-ray uorescence spectrometry 11 are commonly used. However, most of these methods are difficult to be widely used due to economic factors.…”

Section: Introductionmentioning

confidence: 99%