BBI608 induces apoptosis in mucoepidermoid carcinoma cells by targeting a post-transcriptional regulatory mechanisms of myeloid cell leukemia-1.

[OBJECTIVES] BBI608 has demonstrated antitumor activity in several human cancers. However, its efficacy against mucoepidermoid carcinoma (MEC) remains unexplored. This study investigated the antitumor potential of BBI608 in MEC cell lines.

[DESIGN] The antitumor activity of BBI608 in MC3 and YD-15 mucoepidermoid carcinoma (MEC) cell lines was assessed using trypan blue exclusion, Live/Dead, and sphere formation assays. Apoptotic effects were investigated via western blotting, 4',6-diamidino-2-phenylindole (DAPI) staining, Annexin V-fluorescein isothiocyanate/propidium iodide (V-FITC/PI) double staining, and reverse transcription-quantitative PCR.

[RESULTS] BBI608 exhibited growth-inhibitory effects in MEC cell lines, decreasing cell viability and sphere formation capacity while increasing cell death. BBI608-induced apoptosis was confirmed by increased cleaved caspase-3 and PARP expression, nuclear morphological changes characteristic of apoptosis, and increased Annexin V positivity. Furthermore, BBI608 significantly downregulated Mcl-1 expression, which contributed to apoptosis induction in MEC cells. This Mcl-1 downregulation appeared to be mediated by both proteasome-dependent protein degradation and translational regulatory mechanisms in MC3 and YD-15 cells, respectively.

[CONCLUSION] These findings demonstrate that BBI608 effectively inhibits MEC cell proliferation in vitro by inducing Mcl-1-dependent apoptosis. This suggests BBI608 warrants further investigation as a potential therapeutic agent for MEC.