NDLI: The short chain cell-permeable ceramide (C6) restores cell apoptosis and perifosine sensitivity in cultured glioblastoma cells

Content Provider	Springer Nature Link
Author	Qin, Li sen Yu, Zheng quan Zhang, Shi ming Sun, Guan Zhu, Jian Xu, Jin Guo, Jun Fu, Lin shan
Copyright Year	2013
Abstract	Primary glioblastoma multiforme is the most malignant form of astrocytic tumor with an average survival of approximately 12–14 months. The combination of novel Akt inhibitors with anti-cancer therapeutics has achieved improved anti-tumor efficiency. In the current study, we examined the synergistic anti-cancer ability of Akt inhibitor perifosine in combination with short-chain ceramide (C6) against glioblastoma cells (U87MG and U251MG), and studied the underlying mechanisms. We found that perifosine, which blocked Akt/mammalian target of rapamycin activation, only induced moderate cell death and few cell apoptosis in cultured glioblastoma cells. On the other hand, perifosine administration induced significant protective autophagy, which inhibited cell apoptosis induction. Inhibition of autophagy by 3-methyaldenine or by autophagy-related gene-5 RNA interference significantly enhanced perifosine-induced apoptosis and cytotoxicity. We found that the short chain cell-permeable ceramide (C6) significantly enhanced cytotoxic effects of perifosine in cultured glioblastoma cells. For mechanism study, we observed that ceramide (C6) inhibited autophagy induction to restore cell apoptosis and perifosine sensitivity. In conclusion, our study suggests that autophagy inhibition by ceramide (C6) restores perifosine-induced apoptosis and cytotoxicity in glioblastoma cells.
Starting Page	5645
Ending Page	5655
Page Count	11
File Format	PDF
ISSN	03014851
Journal	Molecular Biology Reports
Volume Number	40
Issue Number	10
e-ISSN	15734978
Language	English
Publisher	Springer Netherlands
Publisher Date	2013-09-25
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Glioblastoma Perifosine Ceramide (C6) Autophagy and apoptosis Animal Biochemistry Animal Anatomy / Morphology / Histology
Content Type	Text
Resource Type	Article
Subject	Genetics Medicine Molecular Biology

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