PMID- 20423107
OWN - NLM
STAT- MEDLINE
DCOM- 20100625
LR  - 20211020
IS  - 1520-6025 (Electronic)
IS  - 0163-3864 (Print)
IS  - 0163-3864 (Linking)
VI  - 73
IP  - 5
DP  - 2010 May 28
TI  - The alternative medicine pawpaw and its acetogenin constituents suppress tumor 
      angiogenesis via the HIF-1/VEGF pathway.
PG  - 956-61
LID - 10.1021/np100228d [doi]
AB  - Products that contain twig extracts of pawpaw (Asimina triloba) are widely 
      consumed anticancer alternative medicines. Pawpaw crude extract (CE) and purified 
      acetogenins inhibited hypoxia-inducible factor-1 (HIF-1)-mediated hypoxic 
      signaling pathways in tumor cells. In T47D cells, pawpaw CE and the acetogenins 
      10-hydroxyglaucanetin (1), annonacin (2), and annonacin A (3) inhibited 
      hypoxia-induced HIF-1 activation with IC(50) values of 0.02 microg/mL, 12 nM, 13 
      nM, and 31 nM, respectively. This inhibition correlates with the suppression of 
      the hypoxic induction of HIF-1 target genes VEGF and GLUT-1. The induction of 
      secreted VEGF protein represents a key event in hypoxia-induced tumor 
      angiogenesis. Both the extract and the purified acetogenins blocked the 
      angiogenesis-stimulating activity of hypoxic T47D cells in vitro. Pawpaw extract 
      and acetogenins inhibited HIF-1 activation by blocking the hypoxic induction of 
      nuclear HIF-1alpha protein. The inhibition of HIF-1 activation was associated 
      with the suppression of mitochondrial respiration at complex I. Thus, the 
      inhibition of HIF-1 activation and hypoxic tumor angiogenesis constitutes a novel 
      mechanism of action for these anticancer alternative medicines.
FAU - Coothankandaswamy, Veena
AU  - Coothankandaswamy V
AD  - Department of Pharmacognosy and Research Institute of Pharmaceutical Sciences, 
      School of Pharmacy, University of Mississippi, University, Mississippi 38677, 
      USA.
FAU - Liu, Yang
AU  - Liu Y
FAU - Mao, Shui-Chun
AU  - Mao SC
FAU - Morgan, J Brian
AU  - Morgan JB
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 CA098787-05A2/CA/NCI NIH HHS/United States
GR  - NA16RU1496/PHS HHS/United States
GR  - R01 CA098787-04/CA/NCI NIH HHS/United States
GR  - C06 RR014503/RR/NCRR NIH HHS/United States
GR  - CA98787/CA/NCI NIH HHS/United States
GR  - P20RR021929/RR/NCRR NIH HHS/United States
GR  - P20 RR021929/RR/NCRR 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  - R56 CA098787-05A1/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.
PL  - United States
TA  - J Nat Prod
JT  - Journal of natural products
JID - 7906882
RN  - 0 (Acetogenins)
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (Glucose Transporter Type 1)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Vascular Endothelial Growth Factors)
SB  - IM
MH  - Acetogenins/chemistry/*isolation & purification/*pharmacology
MH  - Antineoplastic Agents, Phytogenic/chemistry/*isolation & 
      purification/*pharmacology
MH  - Asimina/*chemistry
MH  - Complementary Therapies
MH  - Drug Screening Assays, Antitumor
MH  - Glucose Transporter Type 1/analysis/*drug effects/genetics
MH  - Humans
MH  - Hypoxia-Inducible Factor 1/*drug effects
MH  - Inhibitory Concentration 50
MH  - Molecular Structure
MH  - Neovascularization, Physiologic/*drug effects
MH  - Plants, Medicinal/*chemistry
MH  - Vascular Endothelial Growth Factors/analysis/*drug effects/genetics
PMC - PMC2890309
MID - NIHMS200348
EDAT- 2010/04/29 06:00
MHDA- 2010/06/26 06:00
PMCR- 2011/05/28
CRDT- 2010/04/29 06:00
PHST- 2010/04/29 06:00 [entrez]
PHST- 2010/04/29 06:00 [pubmed]
PHST- 2010/06/26 06:00 [medline]
PHST- 2011/05/28 00:00 [pmc-release]
AID - 10.1021/np100228d [doi]
PST - ppublish
SO  - J Nat Prod. 2010 May 28;73(5):956-61. doi: 10.1021/np100228d.