ArticleScientific reports2018
A Functional Signature Ontology (FUSION) screen detects an AMPK inhibitor with selective toxicity toward human colon tumor cells.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 17 citations in OpenAlex.
- High-throughput functional annotation of natural products by integrated activity profiling.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Prescription drugs and mitochondrial metabolism.Bioscience reports · 2022Review
- Tumour Microenvironment Stress Promotes the Development of Drug Resistance.Antioxidants (Basel, Switzerland) · 2021Review
- A Gene Expression High-Throughput Screen (GE-HTS) for Coordinated Detection of Functionally Similar Effectors in Cancer.Cancers · 2020Review
- miR-4999-5p Predicts Colorectal Cancer Survival Outcome and Reprograms Glucose Metabolism by Targeting PRKAA2.OncoTargets and therapy · 2020Article
- Improving natural product research translation: From source to clinical trial.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Synergy and antagonism in natural product extracts: when 1 + 1 does not equal 2.Natural product reports · 2019Review
- Chromomycin AThe Journal of general physiology · 2018Article
- Ethanol and C2 ceramide activate fatty acid oxidation in human hepatoma cells.Scientific reports · 2018Article
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Authors and funding
12 authors at 7 institutions in 3 countries.
Funding
Abstract
AMPK is a serine threonine kinase composed of a heterotrimer of a catalytic, kinase-containing α and regulatory β and γ subunits. Here we show that individual AMPK subunit expression and requirement for survival varies across colon cancer cell lines. While AMPKα1 expression is relatively consistent across colon cancer cell lines, AMPKα1 depletion does not induce cell death. Conversely, AMPKα2 is expressed at variable levels in colon cancer cells. In high expressing SW480 and moderate expressing HCT116 colon cancer cells, siRNA-mediated depletion induces cell death. These data suggest that AMPK kinase inhibition may be a useful component of future therapeutic strategies. We used Functional Signature Ontology (FUSION) to screen a natural product library to identify compounds that were inhibitors of AMPK to test its potential for detecting small molecules with preferential toxicity toward human colon tumor cells. FUSION identified 5'-hydroxy-staurosporine, which competitively inhibits AMPK. Human colon cancer cell lines are notably more sensitive to 5'-hydroxy-staurosporine than are non-transformed human colon epithelial cells. This study serves as proof-of-concept for unbiased FUSION-based detection of small molecule inhibitors of therapeutic targets and highlights its potential to identify novel compounds for cancer therapy development.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.