New 2-aryl-1,4-naphthoquinone-1-oxime methyl ether compound induces microtubule depolymerization and subsequent apoptosis

In this study,we describe the antitumor activity of qo-1,one of the new 2-aryl-1,4-naphthoquinone-1-oxime methyl ether derivatives. qo-1 is a derivative of macarpine,a natural occurring product from rutaceae plant. it could potently inhibit cell growth when tested on 19 cancer cell lines. to investigate its mechanism,two cell lines (hela and mcf-7) sensitive to qo-1 were selected. based on flow cytometry,it was found to induce g2/m-phase arrest. moreover,it could cause microtubule depolymerization both in vitro and in vivo. on the other hand,qo-1 activated spindle assembly checkpoint (sac) proteins. expression of bub1,one of the sac,was gradually increased,reaching a peak after 16 - 20 h,and then gradually decreased. instead,qo-1 increased the sub-g1 population,which suggested a cell death population. actually,expression of bcl-2 family proteins and activation of caspase-3/7 were evidences of apoptosis. consistent with these results,cells with dna fragmentation and multinucleated cells were increased timedependently after qo-1 exposure. in conclusion,qo-1 has promising antitumor effects via microtubule depolymerization. © the japanese pharmacological society.