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].
SSE15206 细胞实验
Cell Line
Concentration
Treated Time
Description
References
A2780-Pac-Res
A2780-Pac-Res
To evaluate the antiproliferative activity of SSE15206 in multidrug-resistant cell lines, results showed that SSE15206 remained highly effective in A2780-Pac-Res cells with a GI50 value of 224.45 ± 21.29 nM.
Sci Rep. 2018 Feb 19;8(1):3305.
KB-V1
KB-V1
To evaluate the antiproliferative activity of SSE15206 in multidrug-resistant cell lines, results showed that SSE15206 remained highly effective in KB-V1 cells with a GI50 value of 354 ± 89.82 nM.
Sci Rep. 2018 Feb 19;8(1):3305.
A549
A549
To evaluate the inhibitory effect of SSE15206 on microtubule polymerization, results showed that SSE15206 effectively inhibited microtubule polymerization.
Sci Rep. 2018 Feb 19;8(1):3305.
HCT116
HCT116
To evaluate the antiproliferative activity of SSE15206, results showed that SSE15206 had significant antiproliferative effects in HCT116 cells with a GI50 value of 197 ± 0.05 nM.
Sci Rep. 2018 Feb 19;8(1):3305.
A2780-Pac-Res cell line
224.45 ± 21.29 nM(GI50)
Evaluate overcoming multidrug resistance, A2780-Pac-Res was not resistant to SSSE15206
Sci Rep. 2018 Feb 19;8(1):3305.
KB-V1
354 ± 89.82 nM(GI50)
Evaluate overcoming multidrug resistance, KB-V1 was sensitive to SSE15206
Sci Rep. 2018 Feb 19;8(1):3305.
A549
1.25 μM and 2.5 μM
Assess microtubule dynamics interference, SSE15206 caused failure of microtubules to repolymerize
Sci Rep. 2018 Feb 19;8(1):3305.
HCT116
197 ± 0.05 nM(GI50)
3 days
Determine half-maximal growth inhibitory (GI50) concentrations, SSE15206 was the most potent compound
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