Differentiation of normal and cancer cells induced by sulfhydryl reduction: biochemical and molecular mechanisms

Differentiation of normal and cancer cells induced by sulfhydryl reduction : biochemical and molecular mechanisms

QC 20100525
We examined the morphological, biochemical and molecular outcome of a nonspecific sulfhydryl reduction in cells, obtained by supplementation of N-acetyl-L-cysteine (NAC) in a 0.1-10 mM concentration range. In human normal primary keratinocytes and in colon and ovary carcinoma cells we obtained evidences for: (i) a dose-dependent inhibition of proliferation without toxicity or apoptosis; (ii) a transition from a proliferative mesenchymal morphology to cell-specific differentiated structures; (iii) a noticeable increase in cell-cell and cell-substratum junctions; (iv) a relocation of the oncogenic beta-catenin at the cell-cell junctions; (v) inhibition of microtubules aggregation; (vi) upregulation of differentiation-related genes including p53, heat shock protein 27 gene, N-myc downstream-regulated gene 1, E-cadherin, and down-regulation of cyclooxygenase-2; (vii) inhibition of c-Src tyrosine kinase. In conclusion, a thiol reduction devoid of toxicity as that operated by NAC apparently leads to terminal differentiation of normal and cancer cells through a pleiade of converging mechanisms, many of which are targets of the recently developed differentiation therapy.

In:Cell Death and Differentiation: Springer Science and Business Media LLC12:10, s. 1285-12961350-90471476-5403

By the author/editor: Parasassi, T.; Brunelli, R.; Bracci-Laudiero, ...; Greco, G.; Gustafsson, A. C ...; Krasnowska, E. K ...; show more...; Lundeberg, Joaki ...; Lundeberg, T.; Pittaluga, E.; Romano, M. C.; Serafino, A.; show less...

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