SSE15206 is a microtubule depolymerizing agent which inhibits microtubule polymerization both in biochemical and cellular assays by binding to colchicine site in tubulin. It causes aberrant mitosis resulting in G2/M arrest due to incomplete spindle formation.
Microtubules are highly dynamic structures that form spindle fibres during mitosis and are one of the most validated cancer targets. SSE15206 is a microtubule polymerization inhibitor with GI50 value of 197 nM in HCT116 cells. SSE15206 also exhibited potent antiproliferative activities against several other cancer cell lines of different origins (leukaemia, breast, lung, and cervical) with sub-micromolar GI50 values. Further, dose-dependent increase in phosphorylation of both histone H3 and MPM2 was observed in CT116 cells following treatment with SSE15206 (0.5 μM, 1 μM and 2 μM) for 4 and 8 hours indicating mitotic arrest. Similarly, treatment with SSE15206 for 8 and 24 hours increased mitotic index (percentage mitotic cells) compared to the DMSO control. Within four hours of treatment with 1 μM SSE15206, CT116 cells started accumulating in the G2/M phase of the cell cycle compared to the DMSO control. The G2/M arrest increased in a time-dependent manner and peaked at 12 hours. Moreover, treatment of three different cell types, HCT116, A549 and CAL-51 with SSE15206 (0.5 μM, 1 μM and 2 μM) for 24 hours, resulted in increased expression of p53 and p21 compared to DMSO control[1].
作用机制
SSE15206 inhibits microtubule polymerization by binding to colchicine site in tubulin[1].
搜索
