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

Abstract

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 non-proliferating cells growing in the presence of the ion, high concentration areas inside the cell were observed. These results support the role of magnesium in the control of cell proliferation, suggesting that mTOR may represent an important target for the antiproliferative effect of magnesium. Selective control of magnesium availability could be a useful strategy for inhibiting osteosarcoma cell growth.

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“…It cannot be applied to cancerous ulcers because of concerns that it causes the proliferation of cancer cells [50]. Further studies are needed to clarify its applicability to cancerous ulcers, as the growth-promoting effect of Mg 2+ treatment has also been reported [16].…”

“…The hydrolysis of ATP by ATPases requires the complex formation of Mg 2+ and ATP [15]. Therefore, Mg 2+ is essential for various cellular responses including cell proliferation, cell cycle, and protein synthesis by both direct and indirect functions [16][17][18].…”

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“…Although Ca 2+ flux measurement is one of the most common applications, other ions like magnesium [87], potassium, sodium [88], and hydrogen [89] can also be monitored using similar techniques.…”

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“…In contrast, when SaOS-2 cells are cultured in magnesium deficiency conditions, the ion remains confined at the plasma membrane, even when the cells are stimulated to grow. This condition is associated with the inhibition of SaOS-2 proliferation [ 12 ].…”