Trichostatin C. A new inducer of differentiation of friend leukemic cells.

Agricultural and Biological Chemistry
1985.0

Abstract

Murine erythroleukemia cells established by Friend et al. are transformed cells blocked in erythropoesis differentiation and serve as a useful model for investigating regulated expression of specialized cell functions. In our screening program for inducers of Friend leukemic cell differentiation, we isolated an active substance 145-A, identified as trichostatin C (an antifungal antibiotic) via ¹H-NMR, IR, UV spectral data, ¹³C-NMR comparison with authentic trichostatin C, and direct sample comparison. Trichostatin C potently induced differentiation of Friend leukemic cells (DS-19) at a concentration range of 100-400 ng/ml (0.2-0.8 μM), with approximately 80% of cells differentiated within 5 days at the optimum concentration (250-300 ng/ml). It also induced Rausher virus-transformed mouse erythroleukemic cells (RV133) into benzidine positive cells at a similar concentration. Compared to other inducers (e.g., chaeotropic agents like HMBA and DMSO requiring high concentrations, or DNA-attacking agents with weak efficiency), trichostatin C characteristically induces erythroid differentiation with high efficiency at a very low concentration. Further studies on the mechanisms of its potent inducing activity are in progress.

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