Cellular Regulation Magnesium
Magnesium and neoplasia: From carcinogenesis to tumor growth and progression or treatment

In memory of our colleague Adam Opolsky
https://doi.org/10.1016/j.abb.2006.02.016Get rights and content

Abstract

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.

Section snippets

Magnesium and the process of carcinogenesis

Magnesium could affect the process of carcinogenesis in two ways: (1) by affecting oxidative stress and consequent oxidative DNA modifications that might lead to mutagenesis; (2) by affecting DNA repair mechanisms which maintain genomic stability.

In vitro data

The role of Mg in the process of cell proliferation has been known for decades. Rubin first described a “coordinate response theory” according to which Mg could influence the growth of eukaryotic cells in vitro through its regulatory role in protein and DNA synthesis [70], [71], [72].

Based upon this rationale we investigated the effect(s) of Mg on tumor cell growth. Tumor cells proved unique in that they showed a limited growth-dependence on Mg availability as compared with normal cells: thus,

Magnesium and angiogenesis

Apart from direct effects on the tumor, Mg may contribute to growth and metastatization by affecting tumor vascularization. It is well known that the relentness growth of a tumor depends on a good blood and nutrient supply [86]. A tumor can grow and, eventually, metastatize only if it induces angiogenesis, i.e., the formation of a new capillary network from pre-existing vessels. While physiological angiogenesis is a highly ordered and regulated process culminating with the organization of a

Magnesium and chemotherapy

Chemotherapy is widely used to reduce tumor size and prevent tumor invasiveness and metastatization. Anticancer drugs can be classified into a number of families based on their biochemical activities or chemical origin. These families include extractive, semisynthetic or pharmaceutically engineered alkylating or intercalating agents, antimetabolites, microtubule inhibitors or stabilizing agents, etc. Alkylating agents, such as cyclophosphamide and melphalan, have one or two electron-deficient

Conclusions

Fig. 3 is aimed at summarizing the available data on the relationship between Mg availability and tumor development which have been described in the previous chapters. Based on this overview, it is clear that Mg availability can be considered more beneficial than detrimental for antagonising tumor development. Magnesium seems to oppose carcinogenesis at least in two ways: (1) by sustaining, if not enhancing, the activity of several DNA repair enzymes; (2) by preventing the oxidative stress

Acknowledgments

Work supported in part by COFIN, 2001064293 and 2003067599; MIUR 60% and linea D1 1990–2005 to F.I.W.; (2002–03) Galileo Project to C.F.C. and F.I.W. and (2002–04) Collaborative Linkage NATO Grant to A.M., J.A.M., and F.I.W.

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    Present address: UMR 866 Différenciation Cellulaire et Croissance, INRA, 34060 Montpellier, France.

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