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

Naunyn-Schmiedeberg's Archives of Pharmacology
Sameh SaberAbdelrahman S Eldin

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...Continue Reading

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Citations

Aug 11, 2020·Naunyn-Schmiedeberg's Archives of Pharmacology·Mahmoud E YoussefYasser M Moustafa
Jul 18, 2021·International Immunopharmacology·Amir Mohamed AbdelhamidRania Ramadan Abdelaziz
Aug 8, 2021·International Journal of Molecular Sciences·Hugo Christian Monroy-RamirezJuan Armendariz-Borunda
Dec 1, 2021·Environmental Science and Pollution Research International·Mahmoud E YoussefSameh Saber
Dec 3, 2021·Biological & Pharmaceutical Bulletin·Yoshie TsujiyaNoboru Okamura

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BETA
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GraphPad

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