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Magnesium is one of a of essential nutrients your body—and every one of its vital organs—needs to work properly and efficiently. Taking enough magnesium is important to avoid magnesium deficiency and the symptoms that come with it.
Try out PMC Labs and tell us what you think. Learn More. To evaluate the effects of magnesium on cancer cells, MgSO 4 and MgCl 2 were screened as magnesium supplements; both forms showed synergistic anticancer effects with AA. Taken together, the of this study suggest that magnesium supplementation enhanced the anticancer effect of AA by inhibiting the hormetic response at a low dose.
This study has also demonstrated that AA treatment with magnesium supplementation provided more effective anticancer therapy than AA treatment alone. However, from the Mayo Clinic showed that the survival time of vitamin C—treated patients was even shorter than that of the placebo group patients [ 4 ]. A ificant difference between those two research groups was the route of AA administration: intravenous injection and oral administration, respectively. To understand the mechanism of AA's anticancer activity, many research groups have treated colon, prostate, leukemia, lymphoma, brain, and stomach cancer cells and chemically or genetically transformed cancer cells with AA and showed cancer growth inhibition and even cancer cell death through hydrogen peroxide—mediated reactive oxygen species ROS generation [  ].
In most cases, the pharmacological concentration of vitamin C required for anticancer effects EC 50 value of 1—10 mM could only be achieved by intravenous administration [ 12 ].
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Thus, to apply [ 13 ] vitamin C as an anticancer therapy, a high intracellular concentration in cancer cells is critically important. In our study, we investigated the hormetic proliferation response of cancer cell lines with low cellular expression levels of sodium-dependent vitamin C transporter family-2 SVCT When a low dose of vitamin C was delivered into such cancer cells, increased proliferation activity was observed [ 13 ].
Because hormetic proliferation of cancer cells occurred on low-dose treatment with vitamin C in cell lines with low SVCT-2 expression, we need to develop a more effective approach for vitamin C anticancer therapy in cells that express little SVCT The close correlation between SVCT-2 expression and the anticancer effects of vitamin C therapy suggests that SVCT-2, which is a key transporter for vitamin C uptake [ 1415 ], could be a potent biomarker for high-dose vitamin C cancer therapy [ 16 ]. In breast and colon cancer cell lines, the anticancer effect of vitamin C showed a positive correlation between the SVCT-2 expression of the cancer cells and intracellular vitamin C concentration [ 16 ].
To prevent a hormetic response during vitamin C treatment and induce vitamin C cancer therapy more effectively, magnesium ion supplementation was recommended to increase the vitamin C uptake activity of SVCT-2 [ 17 ]. Myer's cocktail, which contains vitamins and mineral mixtures including magnesium ionswas developed for use with intravenous vitamin C injections [  ], and it has been broadly used in clinics [ 2122 ]. When Myer's cocktail was first introduced, no information was available about the relationship between magnesium ions and SVCT-2 activity.
Therefore, we have focused on using magnesium ion supplementation with vitamin C cancer therapy to prevent the hormetic response in cancer cell lines with low SVCT-2 levels. In this study, we demonstrated that adding magnesium ions to the vitamin C solution enhanced the anticancer effects of vitamin C by increasing the vitamin C transport activity of SVCT-2 in cancer cell lines with both high and low levels of SVCT Moreover, our show that adding magnesium supplementation to vitamin C cancer therapy could provide more effective cancer therapy and prevent the hormetic response in cancer cells with low SVCT-2 levels.
Which vitamins and minerals should be taken together or separately?
Cells were stained and counted with a cell counting kit-8 Dojindo's Molecular Technologies, Tokyo, Japan. After a h incubation, cell viability was tested.
After three washes in Tris-buffered saline After four washes in Tris-buffered saline Stained cells were observed by confocal microscopy, and images were processed by the Zen black edition program Zeiss. Six hours after treatment with vitamin C and a magnesium supplement, the cells were stained with annexin V and propodium iodine according to the manufacturer's protocolBiolegend. After staining, cells were analyzed on a Guava EasyCyte mini instrument using Cytosoft software version 4.
The mobile phase was provided by Chromsystems, and the experiment was performed according to the instruction manual.
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SUSM facilities are accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International, and all experimental procedures performed here are in accordance with the guidelines of the Institute of Laboratory Animal Resources. The vitamin C and magnesium supplement mixture was injected intraperitoneally every 2 days.
Thirteen days after the first injection, the mice were sacrificed, and the livers were extracted for a vitamin C uptake analysis. Twenty-four hours after treatment, cell viability was measured Figure 1 A and B. The cells showed no cytotoxicity at any of the tested concentrations. However, the cytotoxicity of vitamin C in the two cancer cell lines depended on their SVCT-2 expression levels; higher anticancer effects were shown in MCF-7 cells than in SK-BR-3 cells, with a positive correlation Taking vitamin c and magnesium together SVCT-2 expression levels and the anticancer effects in both cell lines.
Cotreatment with vitamin C and a magnesium supplement showed more effective anticancer activity in cells with low SVCT-2 expression than in cells with high SVCT-2 expression. The expression of SVCT-2 in cancer cells was analyzed using a western blot analysis. We used amine-reactive green fluorescent dye to observe the enhanced anticancer activity of vitamin C according to magnesium supplementation Figure 3 A and B.
The amine-reactive fluorescent dye could not enter live cells but could pass into dead cells. In both cell lines, cells treated with vitamin C plus a magnesium supplement showed more green fluorescence than those that received only vitamin C. Dead cells were stained with green fluorescent dye localized to the cytosol. To analyze the enhanced apoptosis caused by co-treatments of vitamin C and magnesium, annexin V and propodium iodine staining were performed by flow cytometry Figure 4 A and B.
In the culture media supplemented with 5 mM MgSO 4 and MgCl 2the s of dead cells were higher than in the medium containing cells treated only with vitamin C. Cotreatment with vitamin C and magnesium supplement increased late apoptotic response. To investigate the enhanced anticancer effects of vitamin C seen with magnesium supplementation, the amount of vitamin C in the cancer cells was measured by HPLC.
Enhanced anticancer effect of adding magnesium to vitamin c therapy: inhibition of hormetic response by svct-2 activation
Those show that both the cellular uptake of vitamin C and ROS generation increased with magnesium supplementation. Magnesium supplementation enhanced the uptake of vitamin C into cells, which in turn caused more ROS generation. To determine whether the increased uptake of vitamin C was caused by de novo expression levels of SVCT-2, we used a western blot analysis. The western blot analysis also showed that magnesium supplementation enhanced the anticancer effects of vitamin C by inducing more expression of p21 and procaspase-3, which are apoptotic marker proteins Figure 6 A and B. Magnesium supplementation increased cellular uptake of vitamin C and ROS generation.
Western blot analysis for apoptosis response to vitamin C treatment and cotreatment with magnesium ions and vitamin C. Both vitamin C treatment and cotreatment with magnesium ions and vitamin C increased the expression of p21 and the cleavage of caspase However, cotreatment with magnesium ions and vitamin C showed larger increases than vitamin C treatment alone.
Magnesium supplementation enhanced the anticancer effects of vitamin C therapy Figure 2 B and C ; 0. We treated cancer cells with low-dose vitamin C ly shown to induce a hormetic response 0.
Hormetic proliferation response to low-dose vitamin C was inhibited by magnesium supplementation. Cell viability assay from treatment with low-dose vitamin C and magnesium. However, with 5 mM MgCl 2 and MgSO 4the anticancer activity of vitamin C was increased, and the hormetic proliferation response was inhibited.
All of our in vitro data demonstrated that magnesium-supplemented vitamin C treatment prevented the hormetic response and killed cancer cells more effectively than vitamin C treatment alone. Therefore, we extended and applied our findings to an in vivo xenograft mouse model.
The show that cotreating with vitamin C and magnesium ions inhibited tumor growth more effectively than treating with only vitamin C Figure 8 A. Cotreatment with vitamin C and MgCl 2 and MgSO 4 enhanced the anticancer effects of vitamin C in an in vivo xenograft mouse model system. Relative tumor volume of xenograft mouse. The tumor volume of the mice was measured as mm 3.
The vitamin C uptake in the mouse livers was increased by cotreatment with MgCl 2 or MgSO 4confirming the in vitro cell system. Our study demonstrated a hormetic proliferation response to low-dose vitamin C in cancer cell lines with low SVCT-2 expression [ 13 ]. Therefore, we screened the approaches observed to prevent that hormetic response in work [ 13 ].
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One potent approach was treatment with magnesium ions and vitamin C together because magnesium had already been reported as an activator of SVCT-2, which is a vitamin C transporter [ 17 ]. Godoy et al.
Therefore, we applied magnesium ion supplementation to vitamin C cancer therapy. Moreover, ROS generation via dihydrogen peroxide [ 122425 ] also increased because more vitamin C accumulated inside of cancer cells when magnesium was added to vitamin C treatment.
This prooxidant activity of vitamin C led to the breakage of cellular DNA, which interrupted the redox balance and eventually altered the cellular metabolism of cancer cells, such as energy metabolism through NAD depletion [ 2627 ]. Collectively, the strong correlation between this anticancer mechanism of vitamin C and the hormetic response of cancer cells to vitamin C indicates that the amount of cellular uptake of vitamin C might be an important check in the application of vitamin C to cancer therapy.
Magnesium ion supplementation increased the cellular uptake of vitamin C and enhanced the anticancer effects of vitamin C in both in vitro and in vivo systems Figure 2Figure 8. Furthermore, the hormetic proliferation response was inhibited when a magnesium supplement was added to vitamin C treatment in the SK-BR-3 cell line, which has low SVCT-2 expression Figure 7. Other studies have revealed that MgCl 2 interacts with all the exchangers in the cell membrane, whereas MgSO 4 affects only paracellular components [  ]. Myers' cocktail, which includes MgCl 2 and vitamin C, has been used as an auxiliary to high-dose vitamin C cancer therapy [  ].
Vitamin d and magnesium - benefits, dosages, and why they should go together
However, the effect of each ingredient magnesium chloride, calcium gluconate, hydroxocobalamin, pyridoxine hydrochloride, dexpanthenol B complex of Myers' cocktail on cancer cells has not been fully investigated. Therefore, we are here the first to reveal that the magnesium ions in Myers' cocktail are a synergistic anticancer agent with vitamin C treatment.
Various chemotherapeutic agents with vitamin C have been tested as cancer therapy [ 3334 ].