ArticleJournal of experimental & clinical cancer research : CR2021
Targeting AKT with costunolide suppresses the growth of colorectal cancer cells and induces apoptosis in vitro and in vivo.
Article in Journal of experimental & clinical cancer research : CR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 67 citations in OpenAlex.
- Integrating network pharmacology, molecular dynamics, and in vitro assays to unveil the mechanism of costunolide against gastric cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Costunolide, a Sesquiterpene Lactone, Protects Against Platelet Activation and Thrombus Formation.Cells · 2026Article
- Vemurafenib Induces Apoptosis via JNK Activation and AKT Inhibition in Hepatocellular Carcinoma.Journal of Cancer · 2026Article
- Spirulina and exercise: a two-pronged approach to mitigating oxidative stress in colorectal cancer.Molecular biology reports · 2025Review
- Honokiol Inhibits Colorectal Cancer Cell Growth: Involvement of Hsp27 as a Molecular Target.Current issues in molecular biology · 2025Article
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- Costunolide normalizes neuroinflammation and improves neurogenesis deficits in a mouse model of depression through inhibiting microglial Akt/mTOR/NF-κB pathway.Acta pharmacologica Sinica · 2025Article
- Costunolide inhibits the progression of TPA-induced cell transformation and DMBA/TPA-induced skin carcinogenesis by regulation of AKT-mediated signaling.Cancer cell international · 2025Article
- Sesquiterpene Lactones as Promising Phytochemicals to Cease Metastatic Propagation of Cancer.Biomolecules · 2025Review
- The paradigm shift: re-evaluating preclinical animal models for colorectal cancer in the precision medicine era.Frontiers in immunology · 2025Review
- MDFI promotes the proliferation and tolerance to chemotherapy of colorectal cancer cells by binding ITGB4/LAMB3 to activate the AKT signaling pathway.Cancer biology & therapy · 2024Article
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- Conjugates of 3,5-Bis(arylidene)-4-piperidone and Sesquiterpene Lactones Have an Antitumor Effect via Resetting the Metabolic Phenotype of Cancer Cells.Molecules (Basel, Switzerland) · 2024Article
- Alleviating sepsis: Revealing the protective role of costunolide in a cecal ligation and puncture rat model.Iranian journal of basic medical sciences · 2024Article
- P53/MDM2 Complex-Based Targeted Strategies in Colon Adenocarcinoma.Acta medica academica · 2023Article
- Therapeutic Effect of Costunolide in Autoimmune Hepatitis: Network Pharmacology and Experimental Validation.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Investigation of Molecular Mechanisms Involved in Sensitivity to the Anti-Cancer Activity of Costunolide in Breast Cancer Cells.International journal of molecular sciences · 2023Article
- Phytochemicals as Chemo-Preventive Agents and Signaling Molecule Modulators: Current Role in Cancer Therapeutics and Inflammation.International journal of molecular sciences · 2022Review
- Costunolide is a dual inhibitor of MEK1 and AKT1/2 that overcomes osimertinib resistance in lung cancer.Molecular cancer · 2022Article
Corrections and comments
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Authors and funding
16 authors at 7 institutions in 2 countries.
Funding
Abstract
backgroundColorectal cancer (CRC) is a clinically challenging malignant tumor worldwide. As a natural product and sesquiterpene lactone, Costunolide (CTD) has been reported to possess anticancer activities. However, the regulation mechanism and precise target of this substance remain undiscovered in CRC. In this study, we found that CTD inhibited CRC cell proliferation in vitro and in vivo by targeting AKT.
methodsEffects of CTD on colon cancer cell growth in vitro were evaluated in cell proliferation assays, migration and invasion, propidium iodide, and annexin V-staining analyses. Targets of CTD were identified utilizing phosphoprotein-specific antibody array; Costunolide-sepharose conjugated bead pull-down analysis and knockdown techniques. We investigated the underlying mechanisms of CTD by ubiquitination, immunofluorescence staining, and western blot assays. Cell-derived tumour xenografts (CDX) in nude mice and immunohistochemistry were used to assess anti-tumour effects of CTD in vivo.
resultsCTD suppressed the proliferation, anchorage-independent colony growth and epithelial-mesenchymal transformation (EMT) of CRC cells including HCT-15, HCT-116 and DLD1. Besides, the CTD also triggered cell apoptosis and cell cycle arrest at the G2/M phase. The CTD activates and induces p53 stability by inhibiting MDM2 ubiquitination via the suppression of AKT's phosphorylation in vitro. The CTD suppresses cell growth in a p53-independent fashion manner; p53 activation may contribute to the anticancer activity of CTD via target AKT. Finally, the CTD decreased the volume of CDX tumors without of the body weight loss and reduced the expression of AKT-MDM2-p53 signaling pathway in xenograft tumors.
conclusionsOur project has uncovered the mechanism underlying the biological activity of CTD in colon cancer and confirmed the AKT is a directly target of CTD. All of which These results revealed that CTD might be a new AKT inhibitor in colon cancer treatment, and CTD is worthy of further exploration in preclinical and clinical trials.
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Registered trials
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.