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- Title
Perifosine Induces Cell Apoptosis in Human Osteosarcoma Cells: New Implication for Osteosarcoma Therapy?
- Authors
Yao, Chen; Wei, Jian-jun; Wang, Zu-yu; ding, Hui-min; Li, Dong; Yan, Shi-chang; Yang, Yong-jiang; Gu, Zhang-ping
- 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.
- Subjects
BONE cancer; OSTEOSARCOMA; SARCOMA; APOPTOSIS; CANCER cells; HEAT shock proteins; PROGNOSIS; THERAPEUTICS
- Publication
Cell Biochemistry & Biophysics, 2013, Vol 65, Issue 2, p217
- ISSN
1085-9195
- Publication type
Article
- DOI
10.1007/s12013-012-9423-5