Magnesium deficiency inhibits primary tumor growth but favors metastasis in mice

Abstract

The results of several experimental and epidemiological studies have shown an inverse correlation between Mg status and the risk of some cancers. However, relationship between magnesium and cancer is complex. The aim of our work was to examine the precise effect of Mg deficiency on transplantable mouse tumor growth and metastasis. The results obtained indicate a significant retardation of primary tumor growth (up to 70%) in mice receiving Mg-deficient diet. However, Mg repletion caused in these mice significant increase of primary tumor burden. Analysis of cell cycle distribution showed a reduced percentage of cells in the S phase and an increase of cells in the G(0)/G(1) phase of the cell cycle in LLC tumors caused by Mg deficiency. This is in agreement with the effect of low Mg level on cell growth observed in vitro. Interestingly, in mice inoculated with LLC cells and receiving low-magnesium diet, a higher metastatic potential was observed as compared to control mice. In conclusion, our results demonstrate a direct role of magnesium in tumor growth and also point at deleterious effect of low magnesium status on tumor metastasis.

Mineral-enriched deep-sea water inhibits the metastatic potential of human breast cancer cell lines

“…It is presumed that these antitumor activities of DSW may be derived from the combined ionic action of several minerals such as calcium, magnesium and potassium in DSW. Among these minerals, calcium and magnesium may play important roles in mediating the inhibition of metastasis because they are the main mineral ions present in DSW and it was found that deficiency of magnesium and/or calcium levels has been linked to increased risks of cancer and metastasis (6)(7)(8)(9)(10).…”

Magnesium in the Central Nervous System

“…whether Mg deficiency impacts on tumour growth in vivo, a study showed that dietary Mg deprivation inhibited tumour growth in rats by limiting glutathione (GSH) synthesis (Mills et al, 1986), for which Mg is an obligatory cofactor. More recently, in mice subcutaneously injected with Lewis lung carcinoma, mammary adeno--carcinoma and colon carcinoma cells, a low Mg--containing diet was shown to inhibit primary tumour growth, an effect that was promptly reversed by re--introducing Mg in the diet (Nasulewicz et al, 2004). Surprisingly, Mg deficient mice developed far more lung metastases than controls.…”

“…An elevation in free Mg 2+ concentration in capillary endothelial cells increases the proliferation of endothelial cells, restores the cell's ability to generate and utilize ATP for cellular repair mechanisms, and improves disrupted BBB integrity in a variety of insults. In addition to the stimulatory effect of Mg 2+ on endothelial cell migration and proliferation, the observation that high Mg 2+ concentration facilitates the re--endothelialization of vascular injuries may also provide new insights into the role of Mg 2+ in angiogenesis (Maier et al, 2004). A decrease in Mg 2+ level in the microcirculation of the cortical structures causes a rapid and progressive damage to microvessels, leading to focal haemorrhages and brain edema (Altura et al, 1991).…”

“…In both physiological and pathological conditions, Mg 2+ can directly influence BBB properties. Low Mg 2+ concentration in the circulation is associated with increase in endothelial permeability, decrease in vasodilator capacity and an increase in the production of vasoconstrictor substances, cytokines and oxidative products (Touyz, 2003;Maier et al, 2004). In pathological conditions with BBB impairment, Mg 2+ passes into the extracellular compartment of the brain in significantly higher concentrations and plays an important role in the pathophysiological processes that follow BBB disruption.…”

“…Some cellular and molecular aspects were investigated to explain how a low Mg diet inhibited the development of primary tumours while enhancing metastatization. Regarding primary tumours, it is noteworthy that Mg deficiency directly inhibited tumour cell growth by downregulating cyclin B and D3, crucial for the progression through the cell cycle, and by upregulating p21, p27 and Jumonji, all involved in braking cell proliferation (Nasulewicz et al, 2004;. Mg deficiency also affects tumour development indirectly, because it promotes DNA oxidative damage and impairs angiogenesis, one of the hallmarks of cancer (Hanahan and Weinberg, 2000).…”