Sepantronium bromide (YM155; 30 μM) is not sensitive to survivn gene promoter-driven luciferase reporter activity. Sepantronium bromide shows significant supression on endogenous survivin expression in PC-3 and PPC-1 human HRPC cells with deficient p53 via transcriptional inhibition of the survivin gene promoter. Sepantronium bromide (100 nM) does not affect protein expression of c-IAP2, XIAP, Bcl-2, Bcl-xL, Bad, α-actin, and β-tubulin. Sepantronium bromide potently inhibits human cancer cell lines (mutated or truncated p53) such as PC-3, PPC-1, DU145, TSU-Pr1, 22Rv1, SK-MEL-5 and A375 with IC50s ranging from 2.3 to 11 nM, respectively.
Sepantronium bromide (YM155) resultin in an increase in sensitivity of NSCLC cells to γ-radiation. Sepantronium bromide combined with γ-radiation increases both the number of apoptotic cells and the activity of caspase-3. In addition, Sepantronium bromide delays the repair of radiation-induced double-strand breaks in nuclear DNA.