Click
here to close Hello! We notice that
you are using Internet Explorer, which is not supported by Echinobase
and may cause the site to display incorrectly. We suggest using a
current version of Chrome,
FireFox,
or Safari.
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.
Dai J
,
Liu Y
,
Jia H
,
Zhou YD
,
Nagle DG
.
???displayArticle.abstract???
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.
Brastianos,
Exiguamine A, an indoleamine-2,3-dioxygenase (IDO) inhibitor isolated from the marine sponge Neopetrosia exigua.
2006, Pubmed
Brastianos,
Exiguamine A, an indoleamine-2,3-dioxygenase (IDO) inhibitor isolated from the marine sponge Neopetrosia exigua.
2006,
Pubmed
Dai,
Sodwanone and yardenone triterpenes from a South African species of the marine sponge Axinella inhibit hypoxia-inducible factor-1 (HIF-1) activation in both breast and prostate tumor cells.
2006,
Pubmed
Ferrara,
The biology of VEGF and its receptors.
2003,
Pubmed
Guzy,
Oxygen sensing by mitochondria at complex III: the paradox of increased reactive oxygen species during hypoxia.
2006,
Pubmed
Hodges,
Molecular-targeted antitumor agents: the Saururus cernuus dineolignans manassantin B and 4-O-demethylmanassantin B are potent inhibitors of hypoxia-activated HIF-1.
2004,
Pubmed
Hossain,
Saururus cernuus lignans--potent small molecule inhibitors of hypoxia-inducible factor-1.
2005,
Pubmed
Kung,
Suppression of tumor growth through disruption of hypoxia-inducible transcription.
2000,
Pubmed
Kung,
Small molecule blockade of transcriptional coactivation of the hypoxia-inducible factor pathway.
2004,
Pubmed
Maxwell,
Hypoxia-inducible factor-1 modulates gene expression in solid tumors and influences both angiogenesis and tumor growth.
1997,
Pubmed
Melillo,
Targeting hypoxia cell signaling for cancer therapy.
2007,
Pubmed
Moeller,
Pleiotropic effects of HIF-1 blockade on tumor radiosensitivity.
2005,
Pubmed
Mohammed,
Laurenditerpenol, a new diterpene from the tropical marine alga Laurenciaintricata that potently inhibits HIF-1 mediated hypoxic signaling in breast tumor cells.
2004,
Pubmed
Nagle,
Natural product-based inhibitors of hypoxia-inducible factor-1 (HIF-1).
2006,
Pubmed
Ryan,
HIF-1 alpha is required for solid tumor formation and embryonic vascularization.
1998,
Pubmed
Ryan,
Hypoxia-inducible factor-1alpha is a positive factor in solid tumor growth.
2000,
Pubmed
Sakurai,
TMC-256A1 and C1, new inhibitors of IL-4 signal transduction produced by Aspergillus niger var niger TC 1629.
2002,
Pubmed
Semenza,
A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation.
1992,
Pubmed
Semenza,
Development of novel therapeutic strategies that target HIF-1.
2006,
Pubmed
Simon,
Mitochondrial reactive oxygen species are required for hypoxic HIF alpha stabilization.
2006,
Pubmed
Tatum,
Hypoxia: importance in tumor biology, noninvasive measurement by imaging, and value of its measurement in the management of cancer therapy.
2006,
Pubmed
Unruh,
The hypoxia-inducible factor-1 alpha is a negative factor for tumor therapy.
2003,
Pubmed
Zhong,
Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their metastases.
1999,
Pubmed
Zhou,
Terpenoid tetrahydroisoquinoline alkaloids emetine, klugine, and isocephaeline inhibit the activation of hypoxia-inducible factor-1 in breast tumor cells.
2005,
Pubmed
