STX140 and STX641 cause apoptosis via the intrinsic mitochondrial pathway and down-regulate survivin and XIAP expression in ovarian and prostate cancer cells.
Foster PA., Ho YT., Newman SP., Leese MP., Potter BV., Reed MJ., Purohit A.
Many anticancer drugs target microtubules and induce apoptosis. However, improved microtubule-targeting drugs, such as STX140 and STX641, are being developed. These compounds induce cell cycle arrest and apoptosis in a variety of tumour cells. The mechanisms that induce apoptosis and the key mediators involved are elucidated in this study. Results demonstrate that STX140 and STX641 depolarise mitochondrial bioenergetics and activate caspase 3/7 in A2780, LNCaP and MCF-7 cancer cells. Furthermore, both compounds cause a significant reduction in the expression of survivin and XIAP. This work details the temporal organisation of apoptosis induced by two microtubule disruptors and highlights the role that the down-regulation of survivin and XIAP may play in this process.