ArticleOncoTargets and therapy2020
Sinomenine Inhibits Non-Small Cell Lung Cancer via Downregulation of Hexokinases II-Mediated Aerobic Glycolysis.
Article in OncoTargets and therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 35 citations in OpenAlex.
- TCM-Derived Small Molecules Targeting Metabolic Vulnerabilities in NSCLC: Ferroptosis-Centered Mechanisms and Emerging Cuproptosis- and Disulfidptosis-Related Vulnerabilities.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Protein lactylation in metabolic dysfunction-associated steatotic liver disease: a mechanistic review.Diabetology & metabolic syndrome · 2026Review
- Advances in Metabolic Reprogramming and Immune Regulatory Mechanisms in Lung Cancer.Oncology research · 2026Review
- Review
- Metabolomic Insights into Sexual Multi-Morphism of Sinomenine Accumulation inPlants (Basel, Switzerland) · 2025Article
- Targeting the BMI1-Noxa axis by Dioscin induces apoptosis in oral squamous cell carcinoma cells.Journal of Cancer · 2025Article
- Traditional Chinese Medicines as Anticancer Agents for Non-Small Cell Lung Cancer with EGFR Mutations: A Review.Drug design, development and therapy · 2025Review
- Article
- Bioactivities and Mechanisms of Action of Sinomenine and Its Derivatives: A Comprehensive Review.Molecules (Basel, Switzerland) · 2024Review
- FFAR4 activation inhibits lung adenocarcinoma via blocking respiratory chain complex assembly associated mitochondrial metabolism.Cellular & molecular biology letters · 2024Article
- The anti-tumor potential of sinomenine: a narrative review.Translational cancer research · 2023Review
- Sinomenine Hydrochloride Promotes TSHR-Dependent Redifferentiation in Papillary Thyroid Cancer.International journal of molecular sciences · 2022Article
- 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
- Inhibition of LDHA suppresses cell proliferation and increases mitochondrial apoptosis via the JNK signaling pathway in cervical cancer cells.Oncology reports · 2022Article
- Advances in metformin‑based metabolic therapy for non‑small cell lung cancer (Review).Oncology reports · 2022Review
- A new strategy for osteoarthritis therapy: Inhibition of glycolysis.Frontiers in pharmacology · 2022Review
- Natural products targeting glycolytic signaling pathways-an updated review on anti-cancer therapy.Frontiers in pharmacology · 2022Review
- Research Status of Mouse Models for Non-Small-Cell Lung Cancer (NSCLC) and Antitumor Therapy of Traditional Chinese Medicine (TCM) in Mouse Models.Evidence-based complementary and alternative medicine : eCAM · 2022Review
- The role of metabolic ecosystem in cancer progression - metabolic plasticity and mTOR hyperactivity in tumor tissues.Cancer metastasis reviews · 2021Review
- Natural Products, Alone or in Combination with FDA-Approved Drugs, to Treat COVID-19 and Lung Cancer.Biomedicines · 2021Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAddiction to aerobic glycolysis is a common metabolic phenotype in human non-small cell lung cancer (NSCLC). The natural product Sinomenine (Sin) exhibits significant anti-tumor effects in various human cancers. However, the underlying mechanism remains elusive.
methodsThe inhibitory effect of Sin on NSCLC cells was determined by MTS and soft agar assays. The glycolysis efficacy of NSCLC cells was examined by glucose uptake and lactate production. The activation of Akt signaling and the protein level of hexokinases II (HK2) were examined by immunoblot (IB), qRT-PCR, and immunohistochemical staining (IHC). The in vivo anti-tumor effect of Sin was validated by the xenograft mouse model.
resultsWe showed that HK2 is highly expressed in NSCLC tissues and cell lines. Depletion of HK2 suppressed cell viability, anchorage-independent colony formation, and xenograft tumor growth. Sinomenine exhibited a profound inhibitory effect on NSCLC cells by reducing HK2-mediated glycolysis both in vitro and in vivo. Ectopic overexpression of HK2 compromised these anti-tumor efficacies in sinomenine-treated NSCLC cells. Moreover, we revealed that sinomenine decreased Akt activity, which caused the down-regulation of HK2-mediated glycolysis. Knockdown of Akt reduced HK2 protein level and impaired glycolysis. In contrast, overexpression of constitutively activated Akt1 reversed this phenotype.
conclusionThis study suggests that targeting HK2-mediated aerobic glycolysis is required for sinomenine-mediated anti-tumor activity.
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