title: Co-administration of perifosine with paclitaxel synergistically induces apoptosis in ovarian cancer cells: more than just AKT inhibition.
abstract: 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.
authors.affiliation: Central Lab., Jining First People's Hospital, 6 Jiankang Road, Jining City, Shandong Province 272111, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Sun
authors.forename: Teng
authors.initials: T
authors.lastname: Yu
authors.forename: Jinchao
authors.initials: J
authors.lastname: Li
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002518:Ceramides / Q000378:metabolism; D004357:Drug Synergism; D005260:Female; D019073:HT29 Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology*; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002518:Ceramides; D017382:Reactive Oxygen Species; D010767:Phosphorylcholine; C105905:perifosine; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases; C526180:PRKAA1 protein, human; D053148:Caspase 3; D017239:Paclitaxel