Magnesium and neoplasia: From carcinogenesis to tumor growth and progression or treatment
Magnesium is involved in a wide range of biochemical reactions that are crucial to cell proliferation, differentiation, angiogenesis, and apoptosis. Changes in magnesium availability have been shown to influence biological responses of immuno-inflammatory cells. Equally plausible seems to be an involvement of magnesium in the multistep and interconnected processes that lead to tumor formation and development; however, the "how" and "when" of such an involvement remain to be defined. Here, we reviewed in vitro and in vivo data that indicated a role for magnesium in many biological and clinical aspects of cancer (from neoplastic transformation to tumor growth and progression or pharmacologic treatment). In adopting this approach we went through a full circle from molecular aspects to observational or epidemiological studies that could reconcile in a unifying picture the otherwise fragmentary or puzzling data currently available on the role of magnesium in cancer.
Available from: Jacek Kujawski
- "Therein we strongly suggested that the mechanism of cytotoxic activity of these compounds could be related to their ability to adhere to DNA. It is also possible that they can interfere with the cellular Mg 2+ ions that, in turn, participate in many biochemical processes like proliferation, angiogenesis and apoptosis . In a continuation of our attempts to clarify the mechanism of the aforementioned condensed pyrazoles, we present herein our in silico studies concerning potential interactions of these derivatives with some nucleic bases and a DNA chain from the theoretical standpoint. "
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ABSTRACT: In order to verify the previously suggested mechanism of anticancer activity of some dimeric indazole
derivatives basing on the adhesion (or intercalation) to DNA, a simulation of the interactions of
5-(3,5-dimethyl-1H-pyrazol-1-yl)-3-[(4-methylphenyl)sulfonyl]-1H-indazole with guanosine, adenosine,
thymidine, cytidine, and DNA was carried out computationally at the DFT level and analyzed within
ONIOM approaches. Moreover, a similar simulation was executed for a DNA fragment containing the
above bases. The theoretical studies have shown that the interactions may involve both strong and weak
hydrogen bonding arising between the DNA bases nitrogen atoms and the tosyl oxygen and pyrazole
nitrogen atoms, as well as aromatic carbons of the studied indazole derivative.
Available from: PubMed Central
- "Calcium and magnesium ions play a central role in many cellular processes, including muscle contraction, transmitter release, cell proliferation, differentiation, gene transcription, apoptosis, and angiogenesis [1, 2]. Disordered regulation of calcium and magnesium levels may also lead to irregularities in many biological activities, even leading to carcinogenesis. "
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ABSTRACT: Breast cancer is one of the most common cancer and remains the leading cause of cancer-related deaths in women. There is increasing evidence suggesting that TRPM7 plays a pivotal role in breast cancer progression and metastasis. In this study, a case–control study was carried out to investigate the effects of SNPs in TRPM7 genes in the development of breast cancer in Han Population of Northeast China. A total of six SNPs (rs8042919, rs4775899, rs11635825, rs7173321, rs616256, and rs11070795) were chosen and genotyped. Genotypes were analyzed using a single-base primer extension assay. Chi-square (χ
2) test was used to analyze statistical difference between control and patient groups in genotype and allele frequencies. The genotype-specific risks and allele frequencies of haplotypes in breast cancer patients and controls were estimated by OR and 95 % confidence intervals. The G allele of rs8042919 was associated with a reduced disease risk. The G allele of rs7173321 and particularly its homozygous GG genotype are associated with an increased breast cancer risk. Two of the TRPM7 SNPs (rs8042919 and rs7173321) are associated with breast cancer patients in Han Population of Northeast China.
Available from: Barbara Bobrowska
- "The disturbances in minerals homeostasis may induce biochemical changes characteristic of many diseases, including neoplastic diseases . For instance, dietary insufficiencies in selenium, zinc and magnesium elements, and excess intake of copper and iron may increase the cancer risk [2-5]. It was uncovered in many investigations that in mammary malignant tumors an increased copper content is found in comparison with normal tissue and that ceruloplasmin level significantly increases in neoplastic diseases [6-8]. "
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ABSTRACT: The aim of the study was to investigate the effect of dietary supplementation with zinc and polyphenol compounds, i.e. resveratrol and genistein, on the effectiveness of chemically induced mammary cancer and the changes in the content of selected elements (Zn, Cu, Mg, Fe, Ca) in tumors as compared with normal tissue of the mammary gland.
Female Sprague-Dawley rats were divided into study groups which, apart from the standard diet and DMBA (7,12-dimethyl-1,2- benz[a]anthracene), were treated with zinc ions (Zn) or zinc ions + resveratrol (Zn + resveratrol) or zinc ions + genistein (Zn + genistein) via gavage for a period from 40 days until 20 weeks of age. The ICP-OES (inductively coupled plasma optical emission spectrometry) technique was used to analyze the following elements: magnesium, iron, zinc and calcium. Copper content in samples was estimated in an atomic absorption spectrophotometer.
Regardless of the diet (standard; Zn; Zn + resveratrol; Zn + genistein), DMBA-induced breast carcinogenesis was not inhibited. On the contrary, in the Zn + resveratrol supplemented group, tumorigenesis developed at a considerably faster rate. On the basis of quantitative analysis of selected elements we found--irrespectively of the diet applied--great accumulation of copper and iron, which are strongly prooxidative, with a simultaneous considerable decrease of the magnesium content in DMBA-induced mammary tumors. The combination of zinc supplementation with resveratrol resulted in particularly large differences in the amount of the investigated elements in tumors as compared with their content in normal tissue.
Diet supplementation with zinc and polyphenol compounds, i.e. resveratrol and genistein had no effect on the decreased copper level in tumor tissue and inhibited mammary carcinogenesis in the rat. Irrespectively of the applied diet, the development of the neoplastic process in rats resulted in changes of the iron and magnesium content in the cancerous tissue in comparison with the healthy mammary tissue. The application of combined diet supplementation with zinc ions and resveratrol considerably promoted the rate of carcinogenesis and increased the number of DMBA-induced mammary tumors.
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