M2I-1 disrupts the in vivo interaction between CDC20 and MAD2 and increases the sensitivities of cancer cell lines to anti-mitotic drugs via MCL-1s

M2I-1 promotes the sensitivity of cancer cell lines to anti-mitotic drugs. HeLa cells were treated with one of 0.5% DMSO, 50 μM M2I-1, 60 ng/ml nocodazole, or 60 ng/ml nocodazole？+？50 μM M2I-1 in a 24-well plate for 16 h. Digital images of cells from three or four random areas of each well were taken using a digital camera mounted on a tissue culture microscope with a 20x objective lens and used to quantify the mitotic and apoptotic indices. a Sample images showing non-mitotic cells (arrows), normal mitotic cells (arrowheads), mitotically arrested cells (dash line arrows), and apoptotic cells (asterisk). b, d Apoptotic indices quantified from HeLa cells treated with 60 ng/ml (equivalent to 200 nM) nocodazole or 30 nM Taxol under different circumstances as indicated. c, e Mitotic indices quantified from HeLa cells treated with 60 ng/ml nocodazole or 30 nM Taxol under the circumstances indicated. f Apoptotic indices quantified from A549, HT-29 and U2OS cells under the same conditions as described above. All the quantitative data were produced from four independent experiments. n, total cell numbers used for quantification; Noc, nocodazole; M2I-1, MAD2 inhibitor-1. P value: *<？0.017; **< 0.001; ***< 0.0003; ****<？0.000