Insights into the mechanisms involved in magnesium-dependent inhibition of primary tumor growth.
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.
Maier
Jeanette A M
JA
Dipartimento di Scienze Precliniche LITA Vialba, Universita di Milano, Milano, Italy. jeanette.maier@unimi.it
Nasulewicz-Goldeman
Anna
A
Simonacci
Matteo
M
Boninsegna
Alma
A
Mazur
Andrzej
A
Wolf
Federica I
FI
D000818:Animals; D015153:Blotting, Western; D018827:Carcinoma, Lewis Lung / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D052138:Genes, Neoplasm; D006801:Humans; D008274:Magnesium / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D008275:Magnesium Deficiency / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis
D004273:DNA, Neoplasm; D019001:Nitric Oxide Synthase; D008274:Magnesium