Insights Into the Mechanisms Involved in Magnesium-Dependent Inhibition of Primary Tumor Growth

Abstract We have previously shown that a low Magnesium (Mg)-containing diet reversibly inhibits the growth of primary tumors that develop after the injection of Lewis lung carcinoma (LLC) cells in mice. Here we investigate some of the mechanisms responsible for the Mg-dependent regulation of tumor development by studying cell cycle regulation, tumor angiogenesis, and gene expression under Mg deficiency. The inhibition of LLC tumor growth in Mg-deficient mice is due to a direct effect of low Mg on LLC cell proliferation and to an impairment of the angiogenic switch. We also observed an increase of nitric oxide synthesis and oxidative DNA damage. Complementary DNA arrays reveal that Mg deficiency modulates tumor expression of genes involved in the control of cell cycle, stress response, proteolysis, and adhesion. Our results suggest that Mg has multiple and complex roles in tumor development. Acknowledgments and Notes This work was supported by Collaborative Linkage NATO grant to AM, JAM, and FIW (2002–04); COFIN, 2001064293 and 2003067599; MIUR 60% and linea D1 2004–2006 to FIW. Notes a: Abbreviations are as follows: LLC, Lewis lung carcinoma; ECM, extracellular matrix. Membranes of 1176 known genes were used for hybridization (AtlasTM Mouse 1.2 Array and AtlasTM Mouse 1.2 Array Cancer, Clontech, Palo Alto, CA) as described in the Methods. a: Specimens were stained with antibodies against CD31. Data are the mean ± SD of 4 separate experiments. ∗, P < 0.05.