PMID- 23335068
OWN - NLM
STAT- MEDLINE
DCOM- 20130725
LR  - 20211021
IS  - 1559-131X (Electronic)
IS  - 1357-0560 (Linking)
VI  - 30
IP  - 1
DP  - 2013 Mar
TI  - PI-103 sensitizes acute myeloid leukemia stem cells to daunorubicin-induced 
      cytotoxicity.
PG  - 395
LID - 10.1007/s12032-012-0395-5 [doi]
AB  - To date, acute myeloid leukemia (AML) shows very poor outcome for conventional 
      chemotherapy. Leukemia stem cells (LSCs) are insensitive to conventional 
      chemotherapeutic drugs and play a central role in the pathogenesis of AML. 
      Failure to effectively ablate these cells may lead to AML relapse following 
      chemotherapy. Phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of 
      rapamycin (mTOR) signaling pathway is constructively activated in LSCs. This 
      pathway can be inhibited by PI-103, a novel synthesized molecule of the 
      pyridofuropyrimidine class, resulting in the apoptosis of LSCs. Therefore, we 
      investigate the influences of PI-103 in combination with daunorubicin (DNR) on 
      the LSCs. Our data indicate that PI-103 synergistically sensitizes LSCs to 
      DNR-induced cytotoxicity. In addition, the PI-103/DNR co-treatment can induce 
      significant apoptosis in LSCs, but sparing hematopoietic stem cells. The 
      synergistic effect and the LSCs-specific apoptosis mechanism may be associated 
      with the inhibition of PI3K/Akt/mTOR signaling pathway. Our results suggest that 
      PI-103 in combination with DNR may be a potent and less toxic therapy for 
      targeting LSCs and deserve further preclinical and clinical studies in the 
      treatment of AML.
FAU - Ding, Qian
AU  - Ding Q
AD  - Department of Hematology, First Affiliated Hospital of Sun Yat-sen University, 
      Guangzhou, 510080 Guangdong, China.
FAU - Gu, Ran
AU  - Gu R
FAU - Liang, Jiayi
AU  - Liang J
FAU - Zhang, Xiangzhong
AU  - Zhang X
FAU - Chen, Yunxian
AU  - Chen Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130119
PL  - United States
TA  - Med Oncol
JT  - Medical oncology (Northwood, London, England)
JID - 9435512
RN  - 0 (Furans)
RN  - 0 (PI103)
RN  - 0 (Pyridines)
RN  - 0 (Pyrimidines)
RN  - ZS7284E0ZP (Daunorubicin)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Combined Chemotherapy Protocols/*pharmacology
MH  - Apoptosis/drug effects
MH  - Blotting, Western
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Daunorubicin/administration & dosage
MH  - Female
MH  - Flow Cytometry
MH  - Furans/*administration & dosage
MH  - Humans
MH  - *Leukemia, Myeloid, Acute
MH  - Male
MH  - Middle Aged
MH  - Neoplastic Stem Cells/*drug effects
MH  - Pyridines/*administration & dosage
MH  - Pyrimidines/*administration & dosage
MH  - Signal Transduction/drug effects
MH  - Young Adult
EDAT- 2013/01/22 06:00
MHDA- 2013/07/26 06:00
CRDT- 2013/01/22 06:00
PHST- 2012/09/29 00:00 [received]
PHST- 2012/10/05 00:00 [accepted]
PHST- 2013/01/22 06:00 [entrez]
PHST- 2013/01/22 06:00 [pubmed]
PHST- 2013/07/26 06:00 [medline]
AID - 10.1007/s12032-012-0395-5 [doi]
PST - ppublish
SO  - Med Oncol. 2013 Mar;30(1):395. doi: 10.1007/s12032-012-0395-5. Epub 2013 Jan 19.