ArticleNutrients2018
Caffeic Acid Targets AMPK Signaling and Regulates Tricarboxylic Acid Cycle Anaplerosis while Metformin Downregulates HIF-1α-Induced Glycolytic Enzymes in Human Cervical Squamous Cell Carcinoma Lines.
Article in Nutrients, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.
- Research progress of metabolomics in cervical cancer.European journal of medical research · 2023Pooled it
- Aloe vera extract disrupts mitochondrial bioenergetics and suppresses HeLa cervical cancer cell proliferation: Transcriptomic and metabolic insights into cisplatin co-treatment.Journal of bioenergetics and biomembranes · 2026Article
- Natural extracts for the treatment of atherosclerosis.Molecular biology reports · 2026Review
- Purple sweet potato (Ipomoea batatas L. Lam) leaves extract prevents weight gain and lipotoxicity in mice fed a high-fat diet by increasing metabolic flexibility and oxidative metabolism in skeletal muscle and brown adipose tissue.Nutrition & metabolism · 2026Article
- Plant-Derived Modulators of Tumor Metabolism as Novel, Efficacious, and Low-Toxicity Therapeutic Agents for Cancer Treatment.Molecules (Basel, Switzerland) · 2026Review
- ALDOC modulates astrocytic glycolysis and AMPK/mTOR/HIF-1α signaling in Alzheimer's disease.Frontiers in neuroscience · 2026Article
- Mechanism of glycolysis-pyrolysis crosstalk driving vicious circle of intervertebral disc degeneration.Apoptosis : an international journal on programmed cell death · 2025Article
- Phytochemicals as Epigenetic Modulators in Chronic Diseases: Molecular Mechanisms.Molecules (Basel, Switzerland) · 2025Review
- Liensinine reshapes the immune microenvironment and enhances immunotherapy by reprogramming metabolism through the AMPK-HIF-1α axis in hepatocellular carcinoma.Journal of experimental & clinical cancer research : CR · 2025Article
- Yinjia pills inhibits the malignant biological behavior of HeLa cells through PKM2-medicated inhibition of JAK/STAT3 pathway.Cytotechnology · 2025Article
- Anticancer potential of hydroxycinnamic acids: mechanisms, bioavailability, and therapeutic applications.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Clinical research framework proposal for ketogenic metabolic therapy in glioblastoma.BMC medicine · 2024Review
- Review
- Metformin induces ZFP36 by mTORC1 inhibition in cervical cancer-derived cell lines.BMC cancer · 2024Article
- Glucose metabolism reprogramming in gynecologic malignant tumors.Journal of Cancer · 2024Review
- Integrating HPLC-Q-TOF-MS/MS, network pharmacology and experimental validation to decipher the chemical substances and mechanism of modified Gui-shao-liu-jun-zi decoction against gastric cancer.Journal of traditional and complementary medicine · 2023Article
- Article
- Action Mechanism of Metformin and Its Application in Hematological Malignancy Treatments: A Review.Biomolecules · 2023Review
- Impact of AMPK on cervical carcinoma progression and metastasis.Cell death & disease · 2023Article
- Metformin Mitigated Obesity-Driven Cancer Aggressiveness in Tumor-Bearing Mice.International journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The small molecules, natural antioxidant Caffeic Acid (trans-3,4-Dihydroxycinnamic acid CA) and anti-diabetic drug Metformin (Met), activate 5′-adenosine monophosphate-activated protein kinase (AMPK) and interfere with metabolic reprogramming in human cervical squamous carcinoma cells. Here, to gain more insight into the ability of CA, Met and the combination of both compounds to impair aerobic glycolysis (the “Warburg effect”) and disrupt bioenergetics of cancer cells, we employed the cervical tumor cell lines C-4I and HTB-35/SiHa. In epithelial C-4I cells derived from solid tumors, CA alleviated glutamine anaplerosis by downregulation of Glutaminase (GLS) and Malic Enzyme 1 (ME1), which resulted in the reduction of NADPH levels. CA treatment of the cells altered tricarboxylic acid (TCA) cycle supplementation with pyruvate via Pyruvate Dehydrogenase Complex (PDH), increased ROS formation and enhanced cell death. Additionally, CA and CA/Met evoked intracellular energetic stress, which was followed by activation of AMPK and the impairment of unsaturated FA de novo synthesis. In invasive HTB-35 cells, Met inhibited Hypoxia-inducible Factor 1 (HIF-1α) and suppressed the expression of the proteins involved in the “Warburg effect”, such as glucose transporters (
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