PMID- 20929261
OWN - NLM
STAT- MEDLINE
DCOM- 20101230
LR  - 20211020
IS  - 1520-6025 (Electronic)
IS  - 0163-3864 (Print)
IS  - 0163-3864 (Linking)
VI  - 73
IP  - 11
DP  - 2010 Nov 29
TI  - Mammea E/BB, an isoprenylated dihydroxycoumarin protonophore that potently 
      uncouples mitochondrial electron transport, disrupts hypoxic signaling in tumor 
      cells.
PG  - 1868-72
LID - 10.1021/np100501n [doi]
AB  - The mammea-type coumarin mammea E/BB (1) was found to inhibit both 
      hypoxia-induced and iron chelator-induced hypoxia-inducible factor-1 (HIF-1) 
      activation in human breast tumor T47D cells with IC(50) values of 0.96 and 0.89 
      muM, respectively. Compound 1 suppressed the hypoxic induction of secreted VEGF 
      protein (T47D cells) and inhibited cell viability/proliferation in four human 
      tumor cell lines. Compound 1 (at 5 and 20 muM) inhibited human breast tumor 
      MDA-MB-231 cell migration. While the mechanisms that underlie their biological 
      activities have remained unknown, prenylated mammea coumarins have been shown to 
      be cytotoxic to human tumor cells, suppress tumor growth in animal models, and 
      display a wide variety of antimicrobial effects. Mechanistic studies revealed 
      that 1 appears to exert an assemblage of cellular effects by functioning as an 
      anionic protonophore that potently uncouples mitochondrial electron transport and 
      disrupts mitochondrial signaling in human tumor cell lines.
FAU - Du, Lin
AU  - Du L
AD  - Department of Pharmacognosy and Research Institute of Pharmaceutical Sciences, 
      School of Pharmacy, University of Mississippi, University, Mississippi 38677, 
      United States.
FAU - Mahdi, Fakhri
AU  - Mahdi F
FAU - Jekabsons, Mika B
AU  - Jekabsons MB
FAU - Nagle, Dale G
AU  - Nagle DG
FAU - Zhou, Yu-Dong
AU  - Zhou YD
LA  - eng
GR  - R01 CA098787-06/CA/NCI NIH HHS/United States
GR  - C06 RR014503/RR/NCRR NIH HHS/United States
GR  - CA98787/CA/NCI NIH HHS/United States
GR  - C06 RR-14503-01/RR/NCRR NIH HHS/United States
GR  - R01 CA098787/CA/NCI NIH HHS/United States
GR  - R01 CA098787-07/CA/NCI NIH HHS/United States
GR  - R56 CA098787/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20101007
PL  - United States
TA  - J Nat Prod
JT  - Journal of natural products
JID - 7906882
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (Coumarins)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Mammea E-BB compound)
RN  - 0 (Vascular Endothelial Growth Factors)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents, Phytogenic/chemistry/*isolation & 
      purification/*pharmacology
MH  - Coumarins/chemistry/*isolation & purification/*pharmacology
MH  - Disease Models, Animal
MH  - Dominica
MH  - Electron Transport
MH  - Female
MH  - Humans
MH  - Hypoxia-Inducible Factor 1/*drug effects
MH  - Mammea/*chemistry
MH  - Mitochondria/*drug effects/metabolism
MH  - Molecular Structure
MH  - *Plant Bark/chemistry
MH  - Prenylation
MH  - Vascular Endothelial Growth Factors/drug effects
PMC - PMC2993771
MID - NIHMS244125
EDAT- 2010/10/12 06:00
MHDA- 2010/12/31 06:00
PMCR- 2011/11/29
CRDT- 2010/10/09 06:00
PHST- 2010/10/09 06:00 [entrez]
PHST- 2010/10/12 06:00 [pubmed]
PHST- 2010/12/31 06:00 [medline]
PHST- 2011/11/29 00:00 [pmc-release]
AID - 10.1021/np100501n [doi]
PST - ppublish
SO  - J Nat Prod. 2010 Nov 29;73(11):1868-72. doi: 10.1021/np100501n. Epub 2010 Oct 7.