ArticleCell death & disease2017
Oroxylin A suppresses the development and growth of colorectal cancer through reprogram of HIF1α-modulated fatty acid metabolism.
Article in Cell death & disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 87 citations in OpenAlex.
- Hypoxia confers ferroptosis resistance in glioma cells via HIF-1α/SREBP1-mediated regulation of lipid metabolism.Journal of lipid research · 2026Article
- Fatty Acid Metabolism and Hypoxia in the Tumor Microenvironment: Metabolic Adaptation and Clinical Potential in Colorectal Cancer.Biomedicines · 2026Review
- Crosstalk between mFrontiers in immunology · 2026Review
- Obesity-induced metabolic reprogramming of the tumor immune microenvironment: mechanisms, spatial niches, and immunotherapy response.Frontiers in immunology · 2026Review
- The emerging metabolic role and treatment target of CPT1A in CRC.Frontiers in cell and developmental biology · 2026Review
- Lipid metabolic reprogramming in colorectal cancer: Insights to mechanisms and therapeutics.World journal of gastrointestinal oncology · 2025Review
- Identification of GDP as a small inhibitory molecule in HepG2 cells by non‑targeted metabolomics analysis.Oncology letters · 2025Article
- Natural products as metabolic modulators to enhance cancer immunotherapy: reprogramming the tumor microenvironment.Frontiers in immunology · 2025Review
- Metabolic Targets in CRC: The Emerging Role of Cytochrome P450 Inhibitors.Current pharmaceutical design · 2025Review
- Oroxylin A, a broad‑spectrum anticancer agent, relieves monocrotaline‑induced pulmonary arterial hypertension by inhibiting the Warburg effect in rats.Molecular medicine reports · 2024Article
- Natural Products and Derivatives Targeting Metabolic Reprogramming in Colorectal Cancer: A Comprehensive Review.Metabolites · 2024Review
- Mechanisms of drug resistance in nutrient-depleted colorectal cancer cells: insights into lysosomal and mitochondrial drug sequestration.Biology open · 2024Review
- Novel hypoxia- and lactate metabolism-related molecular subtyping and prognostic signature for colorectal cancer.Journal of translational medicine · 2024Article
- Low ACADM expression predicts poor prognosis and suppressive tumor microenvironment in clear cell renal cell carcinoma.Scientific reports · 2024Article
- Deciphering the role of lipid metabolism-related genes in Alzheimer's disease: a machine learning approach integrating Traditional Chinese Medicine.Frontiers in endocrinology · 2024Article
- Combination effect of flavonoids attenuates lung cancer cell proliferation by inhibiting the STAT3 and FAK signaling pathway.Open life sciences · 2024Article
- Lycopene improves autophagy and attenuates carbon tetrachloride-induced hepatic fibrosis in rats.Croatian medical journal · 2023Article
- Anticancer effect of involucrasin A on colorectal cancer cells by modulating the Akt/MDM2/p53 pathway.Oncology letters · 2023Article
- Promising Role of theInternational journal of molecular sciences · 2023Review
- Hypoxic microenvironment in cancer: molecular mechanisms and therapeutic interventions.Signal transduction and targeted therapy · 2023Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The occurrence and progress of colon cancer are closely associated with obesity. Therefore, the lipid metabolism, especially fatty acid metabolism, is a significant section of energy homeostasis in colon cancer cells, and it affects many important cellular processes. Oroxylin A is one of the main bioactive flavonoids of Scutellariae radix, which has a strong anticancer effect but low toxicity to normal tissue. In previous studies, we have proved that oroxylin A reprogrammes metabolism of cancer cells by inhibiting glycolysis. Here, we further investigated the metabolism-modulating effects of oroxylin A on the fatty acid metabolism in colon cancer cells under hypoxia. We found that HIF1α upregulated adipophilin, fatty acid synthase and sterol regulatory element-binding protein 1, and downregulated carnitine palmitoyltransferase 1 (CPT1), resulting in the promoted lipid uptake and transport, increased de novo fatty acid synthesis and suppressed fatty acid oxidation. Oroxylin A inactivated HIF1α and reprogrammed fatty acid metabolism of HCT116 cells, decreasing intracellular fatty acid level and enhancing fatty acid oxidation. Furthermore, the rapid decrease of fatty acid level caused by oroxylin A inhibited the nuclear translocation of β-cantenin and inactivated the Wnt pathway, arousing cell cycle arrest in G2/M phase. In vivo studies demonstrated that high-fat diet increased the incidence of colon cancer and accelerated tumor development. Importantly, besides the growth inhibitory effects on colon cancer xenograft, oroxylin A prevented carcinogenesis and delayed progress of primary colon cancer as well. Our studies enriched the metabolic regulatory mechanism of oroxylin A, and suggested that oroxylin A was a potent candidate for the treatment and prevention of colorectal cancer.
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