PMID- 22123175
OWN - NLM
STAT- MEDLINE
DCOM- 20120601
LR  - 20211021
IS  - 1555-8576 (Electronic)
IS  - 1538-4047 (Print)
IS  - 1538-4047 (Linking)
VI  - 12
IP  - 11
DP  - 2011 Dec 1
TI  - The combination of tephrosin with 2-deoxy-D-glucose enhances the cytotoxicity via 
      accelerating ATP depletion and blunting autophagy in human cancer cells.
PG  - 989-96
LID - 10.4161/cbt.12.11.18364 [doi]
AB  - 2-Deoxy-D-glucose (2-DG), a synthetic glucose analog that acts as a glycolytic 
      inhibitor, is currently under clinical evaluation for targeting tumor cells. 
      Tephrosin (TSN), a plant rotenoid, is known as an anticancer agent. In this 
      study, we describe that the addition of TSN to 2-DG enhanced the cytotoxic 
      activity of 2-DG against various types of cancer cells by accelerating ATP 
      depletion and blunting autophagy. TSN increased the sensitivity of cancer cells 
      to the cytotoxic effect of 2-DG. The combination of TSN and 2-DG induced 
      acceleration of intracellular ATP depletion and the drastic activation of 
      AMP-activated protein kinase (AMPK), which resulted in the inactivation of the 
      mammalian target of rapamycin (mTOR) pathway. Of particular interest, TSN 
      suppressed 2-DG-induced autophagy, a cell survival process in response to 
      nutrient deprivation. We also showed that TSN inhibited 2-DG-induced activation 
      of elongation factor-2 kinase (eEF-2K), which has been known to regulate 
      2-DG-induced autophagy. Inhibition of eEF-2K by RNA interference blunted 
      2-DG-induced autophagy and increased the sensitivity of cancer cells to the 
      cytotoxic effect of 2-DG. The addition of TSN to 2-DG, however, did not enhance 
      the cytotoxic activity of 2-DG by knockdown of eEF-2K, suggesting that inhibition 
      of eEF-2K by tephrsoin could be a critical role in the potentiating effect of TSN 
      on the cytotoxicity of 2-DG. Furthermore, we showed that the blunted autophagy 
      and enhanced cytotoxicity of 2-DG was accompanied by the augmentation of 
      apoptosis. These results show that TSN may be valuable for augmenting the 
      therapeutic efficacy of 2-DG.
FAU - Choi, Yunjin
AU  - Choi Y
AD  - Department of Biochemistry, College of Natural Sciences, Kangwon National 
      University, Chuncheon, Gangwon-Do, South Korea.
FAU - Lee, Jeong-Hyung
AU  - Lee JH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111201
PL  - United States
TA  - Cancer Biol Ther
JT  - Cancer biology & therapy
JID - 101137842
RN  - 03L9OT429T (Rotenone)
RN  - 76-80-2 (tephrosin)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - 9G2MP84A8W (Deoxyglucose)
RN  - EC 2.7.11.20 (Elongation Factor 2 Kinase)
SB  - IM
MH  - Adenosine Triphosphate/*metabolism
MH  - Antineoplastic Combined Chemotherapy Protocols/*toxicity
MH  - Apoptosis/drug effects
MH  - Autophagy/*drug effects
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects
MH  - Deoxyglucose/*toxicity
MH  - Elongation Factor 2 Kinase/metabolism
MH  - Enzyme Activation/drug effects
MH  - Humans
MH  - Intracellular Space/drug effects/metabolism
MH  - Neoplasms/*metabolism
MH  - Rotenone/*analogs & derivatives/toxicity
PMC - PMC3280917
EDAT- 2011/11/30 06:00
MHDA- 2012/06/02 06:00
PMCR- 2012/12/01
CRDT- 2011/11/30 06:00
PHST- 2011/11/30 06:00 [entrez]
PHST- 2011/11/30 06:00 [pubmed]
PHST- 2012/06/02 06:00 [medline]
PHST- 2012/12/01 00:00 [pmc-release]
AID - 18364 [pii]
AID - 2011CBT5061R [pii]
AID - 10.4161/cbt.12.11.18364 [doi]
PST - ppublish
SO  - Cancer Biol Ther. 2011 Dec 1;12(11):989-96. doi: 10.4161/cbt.12.11.18364. Epub 
      2011 Dec 1.