title: Cells derived from normal or cancer breast tissue exhibit different growth properties when deprived of arginine.
abstract: Arginine deprivation impairs cell proliferation more strong in cancer than in normal cells; thus, it has been proposed that such an effect could be exploited for cancer therapy. We have compared the effect of arginine deprivation on normal and cancer cells, studying growth rate, morphology, and protein expression patterns in immortalized human MCF10a cells and in MCF7 cells. Arginine deprivation forces MCF10a cells into irreversible senescence while the vast majority of MCF7 cells become quiescent and resume normal growth following arginine re-addition. Arginine deprivation induced a significant burst of p21cip1 in both cell lines that were reversible in MCF7 and irreversible in MCF10 cells. In the latter cells, p21cip1 increase was accompanied by a time-dependent increase of p16INK4A. Similar effects could be obtained by treating both cell types with α-difluoro-methyl-ornithine, but not with Nω-hydroxy-L-arginine, drugs that interfere specifically but differently with the major pathways of arginine metabolism. Our data suggest that derangement in polyamine synthesis is the main consequence of arginine starvation.
authors.affiliation: Dipartimento di Biologia e Patologia Cellulare e Molecolare L. Califano, University of Naples Federico II, 80131, Naples, Italy. angelachiaviello@libero.it
authors.forename: Angela
authors.initials: A
authors.lastname: Chiaviello
authors.forename: Ida
authors.initials: I
authors.lastname: Paciello
authors.forename: Bianca Maria
authors.initials: BM
authors.lastname: Veneziani
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Palumbo
authors.forename: Salvatore M
authors.initials: SM
authors.lastname: Aloj
mesh_terms: D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D001940:Breast / Q000166:cytology*; D001943:Breast Neoplasms / Q000473:pathology*; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016922:Cellular Senescence; D000518:Eflornithine / Q000494:pharmacology; D005260:Female; D006801:Humans
chemical_list: C068309:N(omega)-hydroxyarginine; D001120:Arginine; D000518:Eflornithine