PMID- 17844994
OWN - NLM
STAT- MEDLINE
DCOM- 20071128
LR  - 20240314
IS  - 0163-3864 (Print)
IS  - 1520-6025 (Electronic)
IS  - 0163-3864 (Linking)
VI  - 70
IP  - 9
DP  - 2007 Sep
TI  - Benzochromenones from the marine crinoid Comantheria rotula inhibit 
      hypoxia-inducible factor-1 (HIF-1) in cell-based reporter assays and 
      differentially suppress the growth of certain tumor cell lines.
PG  - 1462-6
AB  - Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that promotes tumor 
      cell adaptation and survival under hypoxic conditions. HIF-1 is currently 
      recognized as an important molecular target for anticancer drug discovery. The 
      National Cancer Institute open repository of marine invertebrates and algae lipid 
      extracts was evaluated using a T47D breast tumor cell-based reporter assay for 
      HIF-1 inhibitory activity. Bioassay-guided fractionation of an active extract 
      from a crinoid Comantheria rotula yielded seven benzo[g]chromen-4-one and 
      benzo[h]chromen-4-one pigments (1-7). The structures of the new 
      benzo[g]chromenone dimer 9,9'-oxybis-neocomantherin (1) and another new natural 
      pigment 5 were deduced from spectroscopic and spectrometric data. The crinoid 
      pigments significantly inhibited both hypoxia-induced and iron chelator-induced 
      HIF-1 luciferase reporter activity in breast and prostate tumor cells. However, 
      inhibition of HIF-1 in the reporter assay did not translate into a significant 
      decrease in the expression of the downstream HIF-1 target, secreted vascular 
      endothelial growth factor (VEGF). Compound 1 was found to inhibit tumor cell 
      growth in the NCI 60-cell line panel (GI(50) values of 1.6-18.2 microM), and 
      compound 6 produced a unique pattern of tumor cell growth suppression. Five cell 
      lines from different organs were hypersensitive to 6 (GI(50) values of 0.29-0.62 
      microM), and three others were moderately sensitive (GI(50) values of 2.2-5.1 
      microM), while the GI(50) values for most other cell lines ranged from 20 to 47 
      microM. Crinoid benzo[g]chromenones were also found to scavenge radicals in a 
      modified DPPH assay.
FAU - Dai, Jingqiu
AU  - Dai J
AD  - Department of Pharmacognosy, Research Institute of Pharmaceutical Sciences, 
      School of Pharmacy, University of Mississippi, University, Mississippi 
      38677-1848, USA.
FAU - Liu, Yang
AU  - Liu Y
FAU - Jia, Hong
AU  - Jia H
FAU - Zhou, Yu-Dong
AU  - Zhou YD
FAU - Nagle, Dale G
AU  - Nagle DG
LA  - eng
GR  - R01 CA098787/CA/NCI NIH HHS/United States
GR  - R56 CA098787/CA/NCI NIH HHS/United States
GR  - R01 CA098787-02/CA/NCI NIH HHS/United States
GR  - C06 RR014503/RR/NCRR NIH HHS/United States
GR  - C06 RR-14503-01/RR/NCRR 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 - 20070911
PL  - United States
TA  - J Nat Prod
JT  - Journal of natural products
JID - 7906882
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Biphenyl Compounds)
RN  - 0 (Coumarins)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Picrates)
RN  - DFD3H4VGDH (1,1-diphenyl-2-picrylhydrazyl)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/chemistry/*isolation & purification/*pharmacology
MH  - Biphenyl Compounds
MH  - Cell Line, Tumor
MH  - Coumarins/chemistry/*isolation & purification/*pharmacology
MH  - Drug Screening Assays, Antitumor
MH  - Echinodermata/*chemistry
MH  - Hypoxia-Inducible Factor 1/*antagonists & inhibitors
MH  - Marine Biology
MH  - National Cancer Institute (U.S.)
MH  - Papua New Guinea
MH  - Picrates/pharmacology
MH  - United States
PMC - PMC2910718
MID - NIHMS216817
EDAT- 2007/09/12 09:00
MHDA- 2007/12/06 09:00
PMCR- 2010/07/27
CRDT- 2007/09/12 09:00
PHST- 2007/09/12 09:00 [pubmed]
PHST- 2007/12/06 09:00 [medline]
PHST- 2007/09/12 09:00 [entrez]
PHST- 2010/07/27 00:00 [pmc-release]
AID - 10.1021/np070224w [doi]
PST - ppublish
SO  - J Nat Prod. 2007 Sep;70(9):1462-6. doi: 10.1021/np070224w. Epub 2007 Sep 11.