PMID- 24648500
OWN - NLM
STAT- MEDLINE
DCOM- 20141222
LR  - 20211021
IS  - 1757-4684 (Electronic)
IS  - 1757-4676 (Print)
IS  - 1757-4676 (Linking)
VI  - 6
IP  - 5
DP  - 2014 May
TI  - Embelin inhibits endothelial mitochondrial respiration and impairs 
      neoangiogenesis during tumor growth and wound healing.
PG  - 624-39
LID - 10.1002/emmm.201303016 [doi]
AB  - In the normal quiescent vasculature, only 0.01% of endothelial cells (ECs) are 
      proliferating. However, this proportion increases dramatically following the 
      angiogenic switch during tumor growth or wound healing. Recent evidence suggests 
      that this angiogenic switch is accompanied by a metabolic switch. Here, we show 
      that proliferating ECs increasingly depend on mitochondrial oxidative 
      phosphorylation (OxPhos) for their increased energy demand. Under growth 
      conditions, ECs consume three times more oxygen than quiescent ECs and work close 
      to their respiratory limit. The increased utilization of the proton motif force 
      leads to a reduced mitochondrial membrane potential in proliferating ECs and 
      sensitizes to mitochondrial uncoupling. The benzoquinone embelin is a weak 
      mitochondrial uncoupler that prevents neoangiogenesis during tumor growth and 
      wound healing by exhausting the low respiratory reserve of proliferating ECs 
      without adversely affecting quiescent ECs. We demonstrate that this can be 
      exploited therapeutically by attenuating tumor growth in syngenic and xenograft 
      mouse models. This novel metabolic targeting approach might be clinically 
      valuable in controlling pathological neoangiogenesis while sparing normal 
      vasculature and complementing cytostatic drugs in cancer treatment.
FAU - Coutelle, Oliver
AU  - Coutelle O
AD  - Department I for Internal Medicine, University of Cologne, Cologne, Germany.
FAU - Hornig-Do, Hue-Tran
AU  - Hornig-Do HT
FAU - Witt, Axel
AU  - Witt A
FAU - Andree, Maria
AU  - Andree M
FAU - Schiffmann, Lars M
AU  - Schiffmann LM
FAU - Piekarek, Michael
AU  - Piekarek M
FAU - Brinkmann, Kerstin
AU  - Brinkmann K
FAU - Seeger, Jens M
AU  - Seeger JM
FAU - Liwschitz, Maxim
AU  - Liwschitz M
FAU - Miwa, Satomi
AU  - Miwa S
FAU - Hallek, Michael
AU  - Hallek M
FAU - Kronke, Martin
AU  - Kronke M
FAU - Trifunovic, Aleksandra
AU  - Trifunovic A
FAU - Eming, Sabine A
AU  - Eming SA
FAU - Wiesner, Rudolf J
AU  - Wiesner RJ
FAU - Hacker, Ulrich T
AU  - Hacker UT
FAU - Kashkar, Hamid
AU  - Kashkar H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - EMBO Mol Med
JT  - EMBO molecular medicine
JID - 101487380
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Benzoquinones)
RN  - 0 (Uncoupling Agents)
RN  - SHC6U8F5ER (embelin)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/pharmacology/therapeutic use
MH  - Benzoquinones/*pharmacology
MH  - Cell Respiration/*drug effects
MH  - Disease Models, Animal
MH  - Endothelial Cells/*drug effects
MH  - Mice
MH  - Mitochondria/*drug effects/metabolism
MH  - Neoplasms/drug therapy
MH  - *Neovascularization, Pathologic
MH  - Neovascularization, Physiologic/*drug effects
MH  - Uncoupling Agents/*pharmacology/therapeutic use
MH  - Wound Healing/drug effects
PMC - PMC4023885
EDAT- 2014/03/22 06:00
MHDA- 2014/12/23 06:00
PMCR- 2014/05/01
CRDT- 2014/03/21 06:00
PHST- 2014/03/21 06:00 [entrez]
PHST- 2014/03/22 06:00 [pubmed]
PHST- 2014/12/23 06:00 [medline]
PHST- 2014/05/01 00:00 [pmc-release]
AID - emmm.201303016 [pii]
AID - 10.1002/emmm.201303016 [doi]
PST - ppublish
SO  - EMBO Mol Med. 2014 May;6(5):624-39. doi: 10.1002/emmm.201303016.