PMID- 30323898
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230120
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 9
IP  - 71
DP  - 2018 Sep 11
TI  - The Akt/mTOR pathway in cancer stem/progenitor cells is a potential therapeutic 
      target for glioblastoma and neuroblastoma.
PG  - 33549-33561
LID - 10.18632/oncotarget.26088 [doi]
AB  - Nervous system tumors represent some of the highly aggressive cancers in both 
      children and adults, particularly neuroblastoma and glioblastoma. Many studies 
      focused on the pathogenic role of the Akt pathway and the mechanistic target of 
      Rapamycin (mTOR) complex in mediating the progression of various types of cancer, 
      which designates the Akt/mTOR signaling pathway as a master regulator for cancer. 
      Current studies are also elucidating the mechanisms of cancer stem cells (CSCs) 
      in replenishing tumors and explicating the strong correlation between the 
      Akt/mTOR pathway and CSC biology. This instigates the development of novel 
      treatments that target CSCs via inhibiting this pathway to prevent recurrence in 
      various cancer subtypes. In accordance, neuroblastoma and glioblastoma tumors are 
      believed to originate from stem/progenitor cells or dedifferentiated mature 
      neural/glial cells transformed into CSCs, which warrants targeting this 
      subpopulation of CSCs in these tumors. In our study, Triciribine and Rapamycin 
      were used to assess the role of inhibiting two different points of the Akt/mTOR 
      pathway in vitro on U251 (glioblastoma) and SH-SY5Y (neuroblastoma) human cell 
      lines and their CSCs. We showed that both drugs minimally decrease the survival 
      of U251 and SH-SY5Y cells in a 2D model, while this effect was much more 
      pronounced in a 3D culture model. Triciribine and Rapamycin decreased migratory 
      abilities of both cell lines and decreased their sphere-forming units (SFU) by 
      extinguishing their CSC populations. Together, we concluded that Rapamycin and 
      Triciribine proved to be effective in the in vitro treatment of glioblastoma and 
      neuroblastoma, by targeting their CSC population.
FAU - Bahmad, Hisham F
AU  - Bahmad HF
AD  - Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of 
      Medicine, American University of Beirut, Beirut, Lebanon.
FAU - Mouhieddine, Tarek H
AU  - Mouhieddine TH
AD  - Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of 
      Medicine, American University of Beirut, Beirut, Lebanon.
AD  - Current Address: Department of Medical Oncology, Dana-Farber Cancer Institute, 
      Harvard Medical School, Boston, MA, USA.
FAU - Chalhoub, Reda M
AU  - Chalhoub RM
AD  - Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of 
      Medicine, American University of Beirut, Beirut, Lebanon.
AD  - Current Address: Medical Scientist Training Program, College of Medicine, Medical 
      University of South Carolina, Charleston, SC, USA.
FAU - Assi, Sahar
AU  - Assi S
AD  - Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of 
      Medicine, American University of Beirut, Beirut, Lebanon.
FAU - Araji, Tarek
AU  - Araji T
AD  - Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of 
      Medicine, American University of Beirut, Beirut, Lebanon.
FAU - Chamaa, Farah
AU  - Chamaa F
AD  - Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of 
      Medicine, American University of Beirut, Beirut, Lebanon.
FAU - Itani, Muhieddine M
AU  - Itani MM
AD  - Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of 
      Medicine, American University of Beirut, Beirut, Lebanon.
FAU - Nokkari, Amaly
AU  - Nokkari A
AD  - Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American 
      University of Beirut, Beirut, Lebanon.
FAU - Kobeissy, Firas
AU  - Kobeissy F
AD  - Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American 
      University of Beirut, Beirut, Lebanon.
FAU - Daoud, Georges
AU  - Daoud G
AD  - Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of 
      Medicine, American University of Beirut, Beirut, Lebanon.
FAU - Abou-Kheir, Wassim
AU  - Abou-Kheir W
AD  - Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of 
      Medicine, American University of Beirut, Beirut, Lebanon.
LA  - eng
PT  - Journal Article
DEP - 20180911
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
PMC - PMC6173359
OTO - NOTNLM
OT  - cancer stem cell
OT  - glioblastoma
OT  - neuroblastoma
OT  - rapamycin
OT  - triciribine
COIS- CONFLICTS OF INTEREST The authors declare no conflicts of interest.
EDAT- 2018/10/17 06:00
MHDA- 2018/10/17 06:01
PMCR- 2018/09/11
CRDT- 2018/10/17 06:00
PHST- 2018/04/07 00:00 [received]
PHST- 2018/08/23 00:00 [accepted]
PHST- 2018/10/17 06:00 [entrez]
PHST- 2018/10/17 06:00 [pubmed]
PHST- 2018/10/17 06:01 [medline]
PHST- 2018/09/11 00:00 [pmc-release]
AID - 26088 [pii]
AID - 10.18632/oncotarget.26088 [doi]
PST - epublish
SO  - Oncotarget. 2018 Sep 11;9(71):33549-33561. doi: 10.18632/oncotarget.26088. 
      eCollection 2018 Sep 11.