Toxicology in vitro, 2011-04, Vol.25 (3), p.623-629
2011
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- Autor(en) / Beteiligte
- Titel
- l-cysteine as a regulator for arsenic-mediated cancer-promoting and anti-cancer effects
- Ist Teil von
- Toxicology in vitro, 2011-04, Vol.25 (3), p.623-629
- Ort / Verlag
- England: Elsevier Ltd
- Erscheinungsjahr
- 2011
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Previous studies have shown that activities of tyrosine kinases and secretion of the active form of matrix metalloproteinase-2 (MMP-2) are correlated with promotion of tumor growth, while apoptotic cell death in cancer cells is correlated with anti-cancer effects. Although arsenic has been reported to have both cancer-promoting and anti-cancer effects, the mechanisms of the arsenic-mediated bidirectional effects remain unknown. We examined the effects of arsenic on both proto-oncogene c-RET-transfected NIH3T3 cells with benign characters and oncogenic RET-MEN2A-transfected NIH3T3 cells with malignant characters. Arsenic promoted not only c-RET tyrosine kinase activity but also genetically activated RET-MEN2A kinase activity with promotion of dimer formation of RET proteins. Arsenic also increased secretion of the active form of MMP-2 in both RET-MEN2A-transfectants and c-RET-transfectants. On the other hand, arsenic promoted poly-(ADP-ribose) polymerase (PARP) degradation and cell death in both malignant and non-malignant cells. Interestingly, l-cysteine inhibited the arsenic-mediated tumor-promoting effects (activation of kinases and MMP-2 secretion) but not arsenic-mediated anti-cancer effects (PARP degradation and cell death). Our results suggest redox-linked regulation of arsenic-mediated activities of kinases and MMP-2 secretion but not arsenic-mediated cell death. Our results also suggest that l-cysteine is an ideal supplement that inhibits arsenic-mediated tumor-promoting effects without affecting arsenic-mediated anti-cancer effects.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0887-2333eISSN: 1879-3177DOI: 10.1016/j.tiv.2010.12.012Titel-ID: cdi_proquest_miscellaneous_867746139
- Format
- –
- Schlagworte
- Animals, Anticarcinogenic Agents - toxicity, Apoptosis, Arsenic, Arsenites - toxicity, Cancer, Carcinogens, Environmental - toxicity, Cell Survival - drug effects, Cysteine - pharmacology, Drug Interactions, Enzyme Inhibitors - toxicity, l-cysteine, Matrix Metalloproteinase 2 - metabolism, Mice, Multiple Endocrine Neoplasia Type 2a - genetics, NIH 3T3 Cells - drug effects, NIH 3T3 Cells - metabolism, NIH 3T3 Cells - pathology, Poly(ADP-ribose) Polymerases - metabolism, RET tyrosine kinase, Sodium Compounds - toxicity, Transfection