Imbalance of Mg Homeostasis as a Potential Biomarker in Colon Cancer (original) (raw)

Magnesium homeostasis in colon carcinoma LoVo cells sensitive or resistant to doxorubicin

Scientific Reports, 2015

Neoplastic cells accumulate magnesium, an event which provides selective advantages and is frequently associated with TRPM7overexpression. Little is known about magnesium homeostasis in drug-resistant cancer cells. Therefore, we used the colon cancer LoVo cell model and compared doxorubicin-resistant to sensitive cells. In resistant cells the concentration of total magnesium is higher while its influx capacity is lower than in sensitive cells. Accordingly, resistant cells express lower amounts of the TRPM6 and 7, both involved in magnesium transport. While decreased TRPM6 levels are due to transcriptional regulation, post-transcriptional events are involved in reducing the amounts of TRPM7. Indeed, the calpain inhibitor calpeptin markedly increases the levels of TRPM7 in resistant cells. In doxorubicin-sensitive cells, silencing TRPM7 shifts the phenotype to one more similar to resistant cells, since in these cells silencing TRPM7 significantly decreases the influx of magnesium, inc...

Dai Q, Shrubsole MJ, Ness RM, Schlundt D, Cai Q, Smalley WE, Li M, Shyr Y, Zheng WThe relation of magnesium and calcium intakes and a genetic polymorphism in the magnesium transporter to colorectal neoplasia risk. Am J Clin Nutr 86(3): 743-751

American Journal of Clinical Nutrition

Background: Mean magnesium intake in the US population does not differ from that in East Asian populations with traditionally low risks of colorectal cancer and other chronic diseases, but the ratio of calcium to magnesium (Ca:Mg) intake is much higher in the US population. Transient receptor potential melastatin 7 (TRPM7) is a newly found gene essential to magnesium absorption and homeostasis. Objective: We aimed to test whether the association of colorectal polyps with intake of calcium, magnesium, or both and Thr1482Ile polymorphism in the TRPM7 gene is modified by the Ca:Mg intake. Design: Included in the study were a total of 688 adenoma cases, 210 hyperplastic polyp cases, and 1306 polyp-free controls from the Tennessee Colorectal Polyp Study. Results: We found that total magnesium consumption was linked to a significantly lower risk of colorectal adenoma, particularly in those subjects with a low Ca:Mg intake. An inverse association trend was found for hyperplastic polyps. We also found that the common Thr1482Ile polymorphism was associated with an elevated risk of both adenomatous and hyperplastic polyps. Moreover, this polymorphism significantly interacted with the Ca:Mg intake in relation to both adenomatous and hyperplastic polyps. The subjects who carried ͧ1 1482Ile allele and who consumed diets with a high Ca:Mg intake were at a higher risk of adenoma (odds ratio: 1.60; 95% CI: 1.12, 2.29) and hyperplastic polyps (odds ratio: 1.85; 95% CI: 1.09, 3.14) than were the subjects who did not carry the polymorphism. Conclusion: These findings, if confirmed, may provide a new avenue for the personalized prevention of magnesium deficiency and, thus, colorectal cancer.

The relation of magnesium and calcium intakes and a genetic polymorphism in the magnesium transporter to colorectal neoplasia risk

… American journal of …, 2007

Background: Mean magnesium intake in the US population does not differ from that in East Asian populations with traditionally low risks of colorectal cancer and other chronic diseases, but the ratio of calcium to magnesium (Ca:Mg) intake is much higher in the US population. Transient receptor potential melastatin 7 (TRPM7) is a newly found gene essential to magnesium absorption and homeostasis. Objective: We aimed to test whether the association of colorectal polyps with intake of calcium, magnesium, or both and Thr1482Ile polymorphism in the TRPM7 gene is modified by the Ca:Mg intake. Design: Included in the study were a total of 688 adenoma cases, 210 hyperplastic polyp cases, and 1306 polyp-free controls from the Tennessee Colorectal Polyp Study. Results: We found that total magnesium consumption was linked to a significantly lower risk of colorectal adenoma, particularly in those subjects with a low Ca:Mg intake. An inverse association trend was found for hyperplastic polyps. We also found that the common Thr1482Ile polymorphism was associated with an elevated risk of both adenomatous and hyperplastic polyps. Moreover, this polymorphism significantly interacted with the Ca:Mg intake in relation to both adenomatous and hyperplastic polyps. The subjects who carried ͧ1 1482Ile allele and who consumed diets with a high Ca:Mg intake were at a higher risk of adenoma (odds ratio: 1.60; 95% CI: 1.12, 2.29) and hyperplastic polyps (odds ratio: 1.85; 95% CI: 1.09, 3.14) than were the subjects who did not carry the polymorphism. Conclusion: These findings, if confirmed, may provide a new avenue for the personalized prevention of magnesium deficiency and, thus, colorectal cancer.

Magnesium wasting associated with epidermal-growth-factor receptor-targeting antibodies in colorectal cancer: a prospective study

Lancet Oncology, 2007

Background Preliminary evidence suggests that magnesium wasting occurs in patients who are treated with epidermal-growth-factor receptor (EGFR)-targeting antibodies for colorectal cancer. The mechanism of this sideeff ect is unknown, and if all or a subset of patients are aff ected is also unclear. We aimed to assess the incidence, characteristics, and predictive factors of magnesium wasting during treatment with EGFR-targeting antibodies, and to study the pathophysiology of this phenomenon.

Assessment and Imaging of Intracellular Magnesium in SaOS-2 Osteosarcoma Cells and Its Role in Proliferation

Nutrients

Magnesium is an essential nutrient involved in many important processes in living organisms, including protein synthesis, cellular energy production and storage, cell growth and nucleic acid synthesis. In this study, we analysed the effect of magnesium deficiency on the proliferation of SaOS-2 osteosarcoma cells. When quiescent magnesium-starved cells were induced to proliferate by serum addition, the magnesium content was 2–3 times lower in cells maintained in a medium without magnesium compared with cells growing in the presence of the ion. Magnesium depletion inhibited cell cycle progression and caused the inhibition of cell proliferation, which was associated with mTOR hypophosphorylation at Serine 2448. In order to map the intracellular magnesium distribution, an analytical approach using synchrotron-based X-ray techniques was applied. When cell growth was stimulated, magnesium was mainly localized near the plasma membrane in cells maintained in a medium without magnesium. In n...