Aberrant epigenetic modifications are fundamental contributors to the pathogenesis of various
cancers. Consequently, targeting these aberrations with small molecules, such as
histone deacetylase (
HDAC) inhibitors and
DNA methyltransferase (DNMT) inhibitors, presents a viable strategy for
cancer therapy. The objective of this study is to assess the anti-
cancer efficacy of
trichostatin C (
TSC), an analogue of
trichostatin A sourced from the fermentation of Streptomyces sp. CPCC 203909. Our investigations reveal that
TSC demonstrates potent activity against both human
lung cancer and urothelial
bladder cancer cell lines, with IC50 values in the low micromolar range. Moreover,
TSC induces apoptosis mediated by
caspase 3/7 and arrests the cell cycle at the G2/M phase. When combined with the DNMT inhibitor
decitabine,
TSC exhibits a synergistic anti-
cancer effect. Additionally,
protein analysis elucidates a significant reduction in the expression of the
tyrosine kinase receptor Axl. Notably, elevated concentrations of
TSC correlate with the up-regulation of the
transcription factor forkhead box class O1 (FoxO1) and increased levels of the proapoptotic
proteins Bim and p21. In conclusion, our findings suggest
TSC as a promising anti-
cancer agent with HDAC inhibitory activity. Furthermore, our results highlight the potential utility of
TSC in combination with DNMT inhibitors for
cancer treatment.