ERK1/2 activation plays important roles in the opposite effects of Trichostatin A in non-cancer and cancer cells

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.