Chronic exposure to agmatine results in the selection of agmatine-resistant hepatoma cells.

During our study of the cytostatic effect of agmatine, we were able to isolate an agmatine resistant clone from a parental hepatoma cell line, HTC. These cells, called Agres, had slower growth rate than the parental cells when cultured in normal medium. The modification in polyamine content induced by agmatine was much lower in these cells and ornithine decarboxylase, S-adenosylmethionine decarboxylase and spermidine/spermine acetyltransferase activities were much less affected.

Polyamines modulate epithelial-to-mesenchymal transition.

Epithelial-to-mesenchymal transition and mesenchymal-to-epithelial transition are biologic processes responsible for conversion of epithelial cells into a mesenchymal phenotype or viceversa, respectively. They occur during embryo- and foetal-development and, in adult organisms, are involved in wound healing, in the genesis and progression of organ fibrosis as well as in the invasiveness of epithelial cancer cells. The key event of epithelial-to-mesenchymal transition is the loss of E-cadherin expression due to repressor activity of the transcriptional factor Snai1.

Redox mechanisms switch on hypoxia-dependent epithelial-mesenchymal transition in cancer cells.

Epithelial-mesenchymal transition (EMT) and hypoxia are considered as crucial events favouring invasion and metastasis of many cancer cells. In this study, different human neoplastic cell lines of epithelial origin were exposed to hypoxic conditions in order to investigate whether hypoxia per se may trigger EMT programme as well as to mechanistically elucidate signal transduction mechanisms involved. The following human cancer cell lines were used: HepG2 (from human hepatoblastoma), PANC-1 (from pancreatic carcinoma), HT-29 (from colon carcinoma) and MCF-7 (from breast carcinoma).

Beta-catenin triggers nuclear factor kappaB-dependent up-regulation of hepatocyte inducible nitric oxide synthase.

Disruption of cell-to-cell contacts, as observed in many pathophysiological conditions, prime hepatocytes for compensatory hyperplastic response that involves induction of several genes, including proto-oncogenes and other gene targets of beta-catenin signaling pathway. By using cultured hepatocytes and experimental models of adherens junction disruption we have investigated changes in beta-catenin subcellular localization and their relationships with inducible nitric oxide synthase (iNOS) expression. Two experimental models were employed: (a) rat hepatocytes obtained by collagenase liver perfusion within the first 48 h of culture; (b) 48-h old cultured hepatocytes, transiently transfected or not with a plasmid encoding for dominant/negative inhibitory kappa B-alpha, exposed to ethylene glycol-bis-(2-aminoethylether)-N,N,N',N'-tetraacetic acid/LiCl treatment.