ArticleNaunyn-Schmiedeberg's archives of pharmacology2019
Telmisartan attenuates N-nitrosodiethylamine-induced hepatocellular carcinoma in mice by modulating the NF-κB-TAK1-ERK1/2 axis in the context of PPARγ agonistic activity.
Article in Naunyn-Schmiedeberg's archives of pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 34 citations in OpenAlex.
- Hepatic stellate cell inhibition by angiotensin II receptor blocker mitigates liver injury and fibrosis via NF-κB-galectin-3 suppression in a rat nonalcoholic steatohepatitis model.Archives of toxicology · 2025Article
- An Overview of the Role of Peroxisome Proliferator-activated Receptors in Liver Diseases.Journal of clinical and translational hepatology · 2023Review
- Telmisartan-Loaded Lactosylated Chitosan Nanoparticles as a Liver Specific Delivery System: Synthesis, Optimization and Targeting Efficiency.AAPS PharmSciTech · 2023Article
- Antioxidant and anti-inflammatory agents in chronic liver diseases: Molecular mechanisms and therapy.World journal of hepatology · 2023Review
- Protective Effects of Naringin-Dextrin Nanoformula against Chemically Induced Hepatocellular Carcinoma in Wistar Rats: Roles of Oxidative Stress, Inflammation, Cell Apoptosis, and Proliferation.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Peroxisome proliferator-activated receptor gamma as a therapeutic target for hepatocellular carcinoma: Experimental and clinical scenarios.World journal of gastroenterology · 2022Review
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- Electrocardiographic and histopathological characterizations of diabetic cardiomyopathy in rats.Environmental science and pollution research international · 2022Article
- Alkaloids fromEvidence-based complementary and alternative medicine : eCAM · 2022Article
- PPARs as Metabolic Sensors and Therapeutic Targets in Liver Diseases.International journal of molecular sciences · 2021Review
- AKT-AMPKα-mTOR-dependent HIF-1α Activation is a New Therapeutic Target for Cancer Treatment: A Novel Approach to Repositioning the Antidiabetic Drug Sitagliptin for the Management of Hepatocellular Carcinoma.Frontiers in pharmacology · 2021Article
- Roles, molecular mechanisms, and signaling pathways of TMEMs in neurological diseases.American journal of translational research · 2021Review
- The Supportive Role of NSC328382, a P2X7R Antagonist, in Enhancing the Inhibitory Effect of CRID3 on NLRP3 Inflammasome Activation in Rats with Dextran Sodium Sulfate-Induced Colitis.Journal of inflammation research · 2021Article
- Cardioprotective role of GTS-21 by attenuating the TLR4/NF-κB pathway in streptozotocin-induced diabetic cardiomyopathy in rats.Naunyn-Schmiedeberg's archives of pharmacology · 2021Article
- Mebendazole augments sensitivity to sorafenib by targeting MAPK and BCL-2 signalling in n-nitrosodiethylamine-induced murine hepatocellular carcinoma.Scientific reports · 2019Article
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocellular carcinoma (HCC) is characterized by bad prognosis and is the second most common reason for cancer-linked mortality. Treatment with sorafenib (SRF) alone increases patient survival by only a few months. A causal link has been determined between angiotensin II (Ang-II) and HCC. However, the mechanisms underlying the tumorigenic effects of Ang-II remain to be elucidated. N-Nitrosodiethylamine was utilized to examine the effects of telmisartan (TEL) (15 mg/kg), SRF (30 mg/kg), and a combination of these two agents on HCC mice. Downregulation of NF-кBP65 mRNA expression and inhibition of the phosphorylation-induced activation of both ERK1/2 and NF-кB P65 were implicated in the anti-tumor effects of TEL and SRF. Consequent regression of malignant changes and improvements in liver function associated with reduced levels of AFP, TNF-α, and TGF-β1 were also confirmed. Anti-proliferative, anti-metastatic, and anti-angiogenic effects of treatment were indicated by reduced hepatic cyclin D1 mRNA expression, reduced MMP-2 levels, and reduced VEGF levels, respectively. TEL, but not SRF, demonstrated agonistic activity for PPARγ receptors, as evidenced by increased PPARγ DNA binding activity, upregulation of CD36, and HO-1 mRNA expression followed by increased liver antioxidant capacity. Both TEL and SRF inhibited TAK1 phosphorylation-induced activation, indicating that TAK1 might act as a central mediator in the interaction between ERK1/2 and NF-кB. TEL, by modulating the ERK1/2, TAK1, and NF-кB signaling axis in the context of PPARγ agonistic activity, exerted anti-tumor effects and increased tumor sensitivity to SRF. Therefore, TEL is an encouraging agent for further clinical trials regarding the management of HCC.
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