Co-administration of perifosine with paclitaxel synergistically induces apoptosis in ovarian cancer cells: more than just AKT inhibition.

Here we report an oral alkylphospholipid perifosine dramatically sensitizes chemo-resistant ovarian cancer cells to paclitaxel induced cell death and apoptosis in vitro. We found that co-administration perifosine with paclitaxel in human ovarian cancer cells led to the inhibition of AKT/mTOR complex 1 (mTORC1), a marked increase in ceramide and reactive oxygen species (ROS) production, and a striking increase in the activation of pro-apoptosis pathways, including caspase 3, c-Jun N-terminal kinases (JNK) and AMP-activated protein kinase (AMPK). These signaling events together caused a marked increase of cancer cell apoptosis. Combining paclitaxel with perifosine may represent a novel anti-ovarian cancer strategy.