RRC ID 52400
Author Oura K, Tadokoro T, Fujihara S, Morishita A, Chiyo T, Samukawa E, Yamana Y, Fujita K, Sakamoto T, Nomura T, Yoneyama H, Kobara H, Mori H, Iwama H, Okano K, Suzuki Y, Masaki T.
Title Telmisartan inhibits hepatocellular carcinoma cell proliferation in vitro by inducing cell cycle arrest.
Journal Oncol. Rep.
Abstract Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and the third leading cause of cancer-related death. Telmisartan, a widely used antihypertensive drug, is an angiotensin II type 1 (AT1) receptor blocker (ARB) that might inhibit cancer cell proliferation, but the mechanisms through which telmisartan affects various cancers remain unknown. The aim of the present study was to evaluate the effects of telmisartan on human HCC and to assess the expression of microRNAs (miRNAs). We studied the effects of telmisartan on HCC cells using the HLF, HLE, HepG2, HuH-7 and PLC/PRF/5 cell lines. In our experiments, telmisartan inhibited the proliferation of HLF, HLE and HepG2 cells, which represent poorly differentiated types of HCC cells. However, HuH-7 and PLC/PRF/5 cells, which represent well-differentiated types of HCC cells, were not sensitive to telmisartan. Telmisartan induced G0/G1 cell cycle arrest of HLF cells by inhibiting the G0-to-G1 cell cycle transition. This blockade was accompanied by a marked decrease in the levels of cyclin D1, cyclin E and other cell cycle-related proteins. Notably, the activity of the AMP-activated protein kinase (AMPK) pathway was increased, and the mammalian target of rapamycin (mTOR) pathway was inhibited by telmisartan treatment. Additionally, telmisartan increased the level of caspase-cleaved cytokeratin 18 (cCK18), partially contributed to the induction of apoptosis in HLF cells and reduced the phosphorylation of ErbB3 in HLF cells. Furthermore, miRNA expression was markedly altered by telmisartan in vitro. In conclusion, telmisartan inhibits human HCC cell proliferation by inducing cell cycle arrest.
Volume 38(5)
Pages 2825-2835
Published 2017-11
DOI 10.3892/or.2017.5977
PMID 29048654
PMC PMC5780034
MeSH Benzimidazoles / pharmacology* Benzoates / pharmacology* Carcinoma, Hepatocellular / drug therapy Carcinoma, Hepatocellular / genetics* Cell Cycle Checkpoints Cell Cycle Proteins / genetics Cell Line, Tumor Cell Proliferation / drug effects* Gene Expression Regulation, Neoplastic / drug effects Hep G2 Cells Humans Liver Neoplasms / drug therapy Liver Neoplasms / genetics* MicroRNAs / genetics Telmisartan
IF 3.041
Human and Animal Cells Hep G2(RCB1886)