title: ERK1/2 activation plays important roles in the opposite effects of Trichostatin A in non-cancer and cancer cells.
abstract: Histone deacetylase (HDAC) inhibitors are candidates of anti-cancer drugs as they can effectively kill cancer cells while have little or no toxicity to non-cancer cells, but the molecular mechanism underlying this process remains unclear. We previously reported that HDAC inhibitors could protect normal mouse hepatocytes from apoptosis induced by transforming growth factor-β1 (TGF-β1) with the requirement of extracellular signal-regulated kinase 1/2 (ERK1/2). In this study, we investigate the roles of trichostatin A (TSA), a typical HDAC inhibitor, on three non-cancer cell lines AML-12, MDCK and 3T3-L1, and four cancer cell lines Hep-3B, HeLa, A549 and MCF-7. TSA is a fermentation product of Streptomyces originally used as an antifungal agent. Our results showed that TSA blocked not only the TGF-β1-induced apoptosis but also serum starvation-induced apoptosis in all the non-cancer cells, whereas it could induce strong apoptosis in all the cancer cells. Further investigation revealed that TSA can induce the activation of ERK1/2 in the three non-cancer cells but not in the cancer cells. In summary, these findings indicated that TSA protect non-cancer cells from apoptosis via activating ERK1/2, providing a useful insight into the better application of HDAC inhibitors in cancer therapy.
authors.affiliation: Laboratory of Molecular Genetics of Aging and Tumor, Faculty of Life Science and Technology, Kunming University of Science and Technology, 296 Bailongsi Road, Kunming 650224, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Guoyu
authors.initials: G
authors.lastname: Yu
authors.forename: Dongmei
authors.initials: D
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Hu
authors.forename: Weiwei
authors.initials: W
authors.lastname: Lei
mesh_terms: D041721:3T3-L1 Cells; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D004285:Dogs; D004789:Enzyme Activation / Q000187:drug effects*; D005434:Flow Cytometry; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D015151:Immunoblotting; D051379:Mice; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D053773:Transforming Growth Factor beta1; C012589:trichostatin A; D048052:Mitogen-Activated Protein Kinase 3