ArticleOncoTargets and therapy2018
By blocking hexokinase-2 phosphorylation, limonin suppresses tumor glycolysis and induces cell apoptosis in hepatocellular carcinoma.
Article in OncoTargets and therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 53 citations in OpenAlex.
- The moonlighting functions of glycolytic enzymes in tumorigenesis.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Lactylation in cancer: Advances and opportunities for treatment resistance.Clinical and translational medicine · 2025Review
- Bibliometric and visualized analysis of mitophagy in liver cancer from 1998 to 2024.Discover oncology · 2025Article
- Mechanism underlying the effect of Pulsatilla decoction in hepatocellular carcinoma treatment: a network pharmacology and in vitro analysis.BMC complementary medicine and therapies · 2023Article
- Metabolomic Analysis of Phytochemical Compounds from Ethanolic Extract of Lime (Molecules (Basel, Switzerland) · 2023Article
- Natural compounds as lactate dehydrogenase inhibitors: potential therapeutics for lactate dehydrogenase inhibitors-related diseases.Frontiers in pharmacology · 2023Review
- Exploiting the Metabolic Consequences of PTEN Loss and Akt/Hexokinase 2 Hyperactivation in Prostate Cancer: A New Role for δ-Tocotrienol.International journal of molecular sciences · 2022Article
- A Green Extraction Method to Achieve the Highest Yield of Limonin and Hesperidin from Lime Peel Powder (Molecules (Basel, Switzerland) · 2022Article
- Natural products targeting glycolytic signaling pathways-an updated review on anti-cancer therapy.Frontiers in pharmacology · 2022Review
- Limonin induces apoptosis of HL-60 cells by inhibiting NQO1 activity.Food science & nutrition · 2021Article
- CRKL promotes hepatocarcinoma through enhancing glucose metabolism of cancer cells via activating PI3K/Akt.Journal of cellular and molecular medicine · 2021Article
- Development of Potential Antitumor Agents from the Scaffolds of Plant-Derived Terpenoid Lactones.Journal of medicinal chemistry · 2020Article
- Flavonoids against the Warburg phenotype-concepts of predictive, preventive and personalised medicine to cut the Gordian knot of cancer cell metabolism.The EPMA journal · 2020Review
- Role of limonin in anticancer effects of Evodia rutaecarpa on ovarian cancer cells.BMC complementary medicine and therapies · 2020Article
- Supercritical COACS omega · 2020Article
- Dioscin Inhibited Glycolysis and Induced Cell Apoptosis in Colorectal Cancer via Promoting c-myc Ubiquitination and Subsequent Hexokinase-2 Suppression.OncoTargets and therapy · 2020Article
- Limonin: A Review of Its Pharmacology, Toxicity, and Pharmacokinetics.Molecules (Basel, Switzerland) · 2019Review
- Transcription factor Six2 induces a stem cell-like phenotype in renal cell carcinoma cells.FEBS open bio · 2019Article
- Hexokinase II promotes the Warburg effect by phosphorylating alpha subunit of pyruvate dehydrogenase.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2019Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionThe purpose of present study was to investigate the effect of limonin on tumor glycolysis and the underlying mechanisms in hepatocellular carcinoma (HCC).
methodsCell proliferation and colony formation assays were performed to evaluate the potency of limonin against HCC cells in vitro. The glucose consumption and lactate production after limonin treatment was determined. The effect of limonin on hexokinase-2 (HK-2) activity was assessed and the mitochondrial location of HK-2 was studied by immunoprecipitation. Cell apoptosis and protein expression were detected by flow cytometry and western blotting respectively. Protein overexpression by plasmid transfection was adopted to investigate the molecular mechanisms.
resultsHCC proliferation and colony formation were inhibited by limonin in vitro. With the suppression of HK-2 activity, the glycolytic level in HCC cells was substantially reduced, which was evidenced by the decrease of glucose consumption and lactate production. The phosphorylation of HK-2 was substantially inhibited by limonin, which resulted in the disassociation of HK-2 from mitochondria. Due to the reduction of HK-2 in mitochondria, increasing Bax were shifted to the mitochondria and gave rise to the release of cytochrome C, which induced HCC cells to subject to mitochondria-mediated apoptosis. Mechanism investigations revealed that the decrease of HK-2 phosphorylation was mainly due to the inhibition of Akt activity. In Akt exogenously overexpressed HCC cells, limonin-mediated cell proliferation inhibition, glycolysis suppression and apoptosis induction were significantly impaired.
conclusionLimonin inhibited the tumor glycolysis in hepatocellular carcinoma by suppressing HK-2 activity, and the suppression of HK-2 was closely related to the decrease of Akt activity.
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