Telmisartan inhibits hepatocellular carcinoma cell proliferation in vitro by inducing cell cycle arrest

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URI http://shark.lib.kagawa-u.ac.jp/kuir/metadata/28449
Title
Telmisartan inhibits hepatocellular carcinoma cell proliferation in vitro by inducing cell cycle arrest
File
Description

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.

Keywords: hepatocellular carcinoma, telmisartan, cell cycle, angiotensin II type 1 receptor blocker, microRNA

(医博甲678)

Author
著者 大浦 杏子
著者(ヨミ) オオウラ キョウコ
著者(別表記) Oura Kyoko
Publication Title
Oncology Reports
Publication Title Alternative
Oncol Rep.
Volume
38
Issue
5
Start Page
2825
End Page
2835
Publisher
Spandidos Publications
Published Date
2017-09-20
ISSN
1021-335X
NCID
AA11016405
PMID
29048654
DOI
10.3892/or.2017.5977
Resource Type
Thesis or Dissertation
Language
eng
Relation
PMCID: PMC5780034
出版社版DOIリンク(URL): https://doi.org/10.3892/or.2017.5977
Resource URL
https://doi.org/10.3892/or.2017.5977
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5780034/
Rights
Copyright : © Oura et al.
This is an open access article distributed under the terms of Creative Commons Attribution License.
"This is the Publisher's Version of the following article: Telmisartan inhibits hepatocellular carcinoma cell proliferation in vitro by inducing cell cycle arrest; Oncology Reports; Volume 38 Issue 5 (2017) Pages: 2825-2835; doi: 10.3892/or.2017.5977, which has been published in final form at https://doi.org/10.3892/or.2017.5977 . "
Text Version
ETD
Grant ID
博甲第678号
Grant Date
2018-03-24
Degree Name
博士(医学)
Grantor
香川大学
Set
香川大学
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