Differentiation of normal and cancer cells induced by sulfhydryl reduction: biochemical and molecular mechanisms
2005 (English)In: Cell Death and Differentiation, ISSN 1350-9047, E-ISSN 1476-5403, Vol. 12, no 10, 1285-1296 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2005. Vol. 12, no 10, 1285-1296 p.
colon carcinoma, cyclooxygenase-2, junctions, ovary carcinoma, proliferation, c-Src, redox regulation, src kinase, colorectal-cancer, n-acetylcysteine, colon-cancer, dna-damage, stem-cells, gene, apoptosis, cytoskeleton
IdentifiersURN: urn:nbn:se:kth:diva-15035DOI: 10.1038/sj.cdd.4401663ISI: 000231805600004ScopusID: 2-s2.0-26844471893OAI: oai:DiVA.org:kth-15035DiVA: diva2:333076
QC 201005252010-08-052010-08-05Bibliographically approved