ArticleJournal of advanced research2025
Dehydrocostus lactone suppresses gastric cancer progression by targeting ACLY to inhibit fatty acid synthesis and autophagic flux.
Article in Journal of advanced research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 34 citations in OpenAlex.
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- ACSL3 inhibits ferroptosis in gastric cancer through the activation of unfolded protein response following endoplasmic reticulum stress.Cell death & disease · 2026Article
- Dehydrocostus lactone attenuates hepatic steatosis by regulating fatty acid oxidation and lipid metabolism: integrated transcriptomic and metabolomic analysis.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Silencing of ELFN1-AS1 induces prostate cancer cell apoptosis and autophagy by regulating miR-28-5p/BCAM axis.World journal of surgical oncology · 2026Article
- Hypoxia/lactate orchestrates the reprogramming metabolism of lung adenocarcinoma by modulating the SIRT2-mediated acetylation.Journal of translational medicine · 2026Article
- Cis-3-hexen-1-ol suppresses bladder cancer progression by inducing mitophagy via the PCK2/AMPK/mTOR signaling pathway.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Fatty acid β-oxidation-associated prognostic model in gastric cancer and functional validation of IL-6 as a potential therapeutic target.Scientific reports · 2026Article
- Enhancing platinum-based chemotherapy efficacy and safety through combination therapy-mediated remodeling of autophagic homeostasis in gastric cancer.Cell death & disease · 2026Article
- Conventional and Novel Approaches to Establishing Mouse Models of Gastric Cancer in the Past, Present, and Potential Post-H. Pylori Infection Era.Biological procedures online · 2026Review
- Article
- Unraveling autophagy-metabolism crosstalk in cancer: Molecular insights and therapeutic strategies.Theranostics · 2026Review
- Exploring Lipid Metabolic Reprogramming: Mechanistic Insights and Implications for Tumor Radiotherapy.International journal of biological sciences · 2026Review
- Targeting the remodeled peritoneal ecosystem: a paradigm shift from tumor cells to the microenvironment in gastric cancer peritoneal metastasis.Frontiers in immunology · 2026Review
- Deacetylation of ACLY Mediates RNA MAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Synergistic Promotion of Triple-Negative Breast Cancer Tumorigenesis and Metastasis by Oral Polystyrene Nanoplastics Exposure via Alloprevotella-Derived Glutamate and Platelet Activation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Pharmacological induction of acetyl-CoA carboxylase 1 autophagic degradation attenuates lipid accumulation and cholangiocarcinoma progression.Journal of experimental & clinical cancer research : CR · 2025Article
- Radiotherapy affects the ELAVL1-mediated autophagy pathway by promoting the release of LINC01943 exosomes in breast cancer cells to accelerate the M2 polarization of macrophages.Medical oncology (Northwood, London, England) · 2025Article
- Nephroprotective mechanism of Kunkui Baoshen decoction in diabetic kidney disease: Targeting the HERC2/NCOA4-mediated autophagy-dependent ferroptosis pathway.World journal of diabetes · 2025Article
- In-situ-formed TCM-inspired dual-function nanocomposite hydrogel for intraoperative hemostasis and postoperative recurrence prevention in hepatocellular carcinoma.Materials today. Bio · 2025Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionDehydrocostus lactone (Dehy), a natural sesquiterpene lactone from Saussurea lappa Clarke, displays remarkable efficacy in treating cancer and gastrointestinal disorders. However, its anti-gastric cancer (GC) effect remains poorly understood.
objectivesOur study aimed to elucidate the anti-GC effect of Dehy and its putative mechanism.
methodsThe anti-GC effect was assessed with MTT, colony formation, wound healing and transwell invasion assays. Cell apoptosis rate was detected by Annexin V-FITC/PI binding assay. Network pharmacology analysis and XF substrate oxidation stress test explored the underlying mechanism and altered metabolic phenotype. Lipogenic enzyme expressions and neutral lipid pool were measured to evaluate cellular lipid synthesis and storage. Biolayer interferometry and molecular docking investigated the direct target of Dehy. Autophagosomes were observed by transmission electron microscopy and MDC staining, while the autophagic flux was detected by mRFP-GFP-LC3 transfection. The clinical significance of ACLY was confirmed by tissue microarrays. Patient-derived xenograft (PDX) models were adopted to detect the clinical therapeutic potential of Dehy.
resultsDehy prominently suppressed GC progression both in vitro and in vivo. Mechanistically, Dehy down-regulated the lipogenic enzyme ACLY, thereby reducing fatty acid synthesis and lipid reservation. Moreover, IKKβ was identified as the direct target of Dehy. Dehy inhibited the phosphorylation of IKKβ, promoting the ubiquitination and degradation of ACLY, thereby resulting in lipid depletion. Subsequently, GC cells initiated autophagy to replenish the missing lipids, whereas Dehy impeded this cytoprotective mechanism by down-regulating LAMP1 and LAMP2 expressions, which disrupted lysosomal membrane functions, ultimately leading to apoptosis. Additionally, Dehy exhibited potential in GC clinical therapy as it enhanced the efficacy of 5-Fluorouracil in PDX models.
conclusionsOur work identified Dehy as a desirable agent for blunting abnormal lipid metabolism and highlighted its inhibitory effect on protective autophagy, suggesting the future development of Dehy as a novel therapeutic drug for GC.
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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 Socratic graph.