title: Perifosine induces cell apoptosis in human osteosarcoma cells: new implication for osteosarcoma therapy?
abstract: Despite the advances of adjuvant chemotherapy and significant improvement of survival, the prognosis for patients with osteosarcoma is generally poor. The search for more effective anti-osteosarcoma agents is necessary and urgent. Here we report that perifosine induces cell apoptosis and growth inhibition in cultured human osteosarcoma cells. Perifosine blocks Akt/mTOR complex 1 (mTORC1) signaling, while promoting caspase-3, c-Jun N-terminal kinases (JNK), and p53 activation. Further, perifosine inhibits survivin expression probably by disrupting its association with heat shock protein-90 (HSP-90). These signaling changes together were responsible for a marked increase of osteosarcoma cell apoptosis and growth inhibition. Finally, we found that a low dose of perifosine enhanced etoposide- or doxorubicin-induced anti-OS cells activity. The results together suggest that perifosine might be used as a novel and effective anti-osteosarcoma agent.
authors.affiliation: Department of Orthopedics, BenQ Medical Center, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Yao
authors.forename: Jian-jun
authors.initials: JJ
authors.lastname: Wei
authors.forename: Zu-yu
authors.initials: ZY
authors.lastname: Wang
authors.forename: Hui-min
authors.initials: HM
authors.lastname: Ding
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.forename: Shi-chang
authors.initials: SC
authors.lastname: Yan
authors.forename: Yong-jiang
authors.initials: YJ
authors.lastname: Yang
authors.forename: Zhang-ping
authors.initials: ZP
authors.lastname: Gu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology; D004357:Drug Synergism; D004797:Enzyme-Linked Immunosorbent Assay; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000378:metabolism; D012516:Osteosarcoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D046912:Multiprotein Complexes; D016159:Tumor Suppressor Protein p53; D010767:Phosphorylcholine; C105905:perifosine; D005047:Etoposide; D004317:Doxorubicin; D000076222:Mechanistic Target of Rapamycin Complex 1; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D053148:Caspase 3