PMID- 26788210
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210927
IS  - 1792-1074 (Print)
IS  - 1792-1082 (Electronic)
IS  - 1792-1074 (Linking)
VI  - 10
IP  - 6
DP  - 2015 Dec
TI  - Inhibition of tumor necrosis factor-alpha enhances apoptosis induced by nuclear 
      factor-kappaB inhibition in leukemia cells.
PG  - 3793-3798
AB  - Inhibition of nuclear factor-kappaB (NF-kappaB) results in antitumor activity in leukemia 
      cells, and may be a potential therapeutic strategy for the treatment of leukemia. 
      However, a significant limitation of NF-kappaB inhibition in the treatment of 
      leukemia is the low efficiency of this technique. NF-kappaB inhibitor treatment 
      induces apoptosis in leukemia cells; however, it additionally causes inflammatory 
      molecules to induce increased sensitivity of healthy hematopoietic cells to cell 
      death signals, therefore limiting its clinical applications. Tumor necrosis 
      factor-alpha (TNF-alpha) is a key regulator of inflammation, and induces a variety of 
      actions in leukemic and healthy hematopoietic cells. TNF-alpha induces 
      NF-kappaB-dependent and -independent survival signals, promoting the proliferation of 
      leukemia cells. However, in healthy hematopoietic cells, TNF-alpha induces death 
      signaling, an effect which is enhanced by the inhibition of NF-kappaB. Based on these 
      observations, the present study hypothesized that inhibition of TNF-alpha signaling 
      may be able to protect healthy hematopoietic cells and other tissue cells, while 
      increasing the anti-leukemia effects of NF-kappaB inhibition on leukemia cells. The 
      role and underlying molecular mechanisms of TNF-alpha inhibition in the regulation of 
      NF-kappaB inhibition-induced apoptosis in leukemia cells was therefore investigated 
      in the present study. The results indicated that inhibition of TNF-alpha enhanced 
      NF-kappaB inhibition-induced apoptosis in leukemia cells. It was also revealed that 
      protein kinase B was significant in the regulation of TNF-alpha and NF-kappaB 
      inhibition-induced apoptosis. During this process, intrinsic apoptotic pathways 
      were activated. A combination of NF-kappaB and TNF-alpha inhibition may be a potential 
      specific and effective novel therapeutic strategy for the treatment of leukemia.
FAU - Dong, Qiao-Mei
AU  - Dong QM
AD  - Central Laboratory, The First Hospital of Lanzhou University, Lanzhou, Gansu 
      730000, P.R. China.
FAU - Ling, Chun
AU  - Ling C
AD  - Central Laboratory, The First Hospital of Lanzhou University, Lanzhou, Gansu 
      730000, P.R. China.
FAU - Chen, Xuan
AU  - Chen X
AD  - Central Laboratory, The First Hospital of Lanzhou University, Lanzhou, Gansu 
      730000, P.R. China.
FAU - Zhao, L I
AU  - Zhao LI
AD  - Central Laboratory, The First Hospital of Lanzhou University, Lanzhou, Gansu 
      730000, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20151008
PL  - Greece
TA  - Oncol Lett
JT  - Oncology letters
JID - 101531236
PMC - PMC4665719
OTO - NOTNLM
OT  - apoptosis
OT  - caspase 9
OT  - leukemia
OT  - molecular mechanism
OT  - nuclear factor-kappaB inhibition
OT  - protein kinase B
OT  - tumor necrosis factor alpha
EDAT- 2016/01/21 06:00
MHDA- 2016/01/21 06:01
PMCR- 2015/10/08
CRDT- 2016/01/21 06:00
PHST- 2014/07/21 00:00 [received]
PHST- 2015/09/14 00:00 [accepted]
PHST- 2016/01/21 06:00 [entrez]
PHST- 2016/01/21 06:00 [pubmed]
PHST- 2016/01/21 06:01 [medline]
PHST- 2015/10/08 00:00 [pmc-release]
AID - OL-0-0-3786 [pii]
AID - 10.3892/ol.2015.3786 [doi]
PST - ppublish
SO  - Oncol Lett. 2015 Dec;10(6):3793-3798. doi: 10.3892/ol.2015.3786. Epub 2015 Oct 8.