Inhibition of hypoxia inducible factor-2 transcription: isolation of active modulators from marine sponges
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Updated: May 19, 2026
Induction and Testing of Hypoxia in Cell Culture
Published on: August 12, 2011
Tawnya C McKee1, Daniel Rabe, Heidi R Bokesch
1Molecular Targets Laboratory, Center for Cancer Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland 21702, USA. mckeeta@mail.nih.gov
Abstract:
Renal or kidney cancer accounts for about 3% of all cancer cases reported each year in the U.S. Molecular signatures that define the cancer, such as the loss of functional VHL, are found in both sporadic and familial cases of cancer. In clear cell renal cancer, the transcription factor HIF-2α has been shown to have a distinct role in tumorigenesis. Our laboratories developed a cell-based screen to identify modulators of HIF-2α. Screening of the NCI's Natural Product Extract Repository resulted in the identification of 10 sponge extracts, from which 12 compounds were isolated. The biological evaluation of these compounds will be discussed including evaluation of HIF-1α vs HIF-2α selectivity and the isolated compounds' effects on mRNA from several pathways regulated by HIF.
Insights
Researchers screened natural products to find compounds that modulate Hypoxia-Inducible Factor-2 alpha (HIF-2α), a key factor in clear cell renal cancer development. This study identified 12 compounds from sponge extracts with potential anti-cancer properties.
Area of Science:
- Oncology
- Molecular Biology
- Natural Product Chemistry
Background:
- Renal cancer constitutes approximately 3% of annual U.S. cancer diagnoses.
- Loss of functional VHL is a molecular hallmark in both sporadic and familial kidney cancers.
- Hypoxia-Inducible Factor-2 alpha (HIF-2α) plays a critical role in clear cell renal cancer tumorigenesis.
Purpose of the Study:
- To develop a cell-based screening assay for identifying modulators of HIF-2α.
- To discover novel compounds targeting HIF-2α from natural sources.
Main Methods:
- A cell-based screen was established to identify HIF-2α modulators.
- The NCI's Natural Product Extract Repository was screened.
- 10 sponge extracts were identified, leading to the isolation of 12 compounds.
Main Results:
- 12 compounds were isolated from 10 sponge extracts.
- Biological evaluation focused on HIF-1α vs. HIF-2α selectivity.
- The effects of isolated compounds on HIF-regulated mRNA were assessed.
Conclusions:
- Natural product screening identified potential HIF-2α modulators from marine sponges.
- These compounds warrant further investigation for their therapeutic potential in renal cancer.
- Understanding HIF-2α's role is crucial for developing targeted clear cell renal cancer therapies.
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