The angiotensin II type 1 receptor antagonist telmisartan inhibits cell proliferation and tumor growth of esophageal adenocarcinoma via the AMPKα/mTOR pathway<i>in vitro</i>and<i>in vivo</i>

Fujihara, Shintaro; Morishita, Asahiro; Ogawa, Kazufumi; Tadokoro, Tomoko; Chiyo, Taiga; Kato, Kiyohito; Kobara, Hideki; Mori, Hideki; Iwama, Hisakazu; Masaki, Tsutomu

doi:10.18632/oncotarget.14345

Cited by 40 publications

(61 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The main mechanism associated with antitumor effect by telmisartan treatment has been shown to inhibit cell proliferation by inducing apoptosis in various cancer cell lines, including prostate ( 8 ), renal ( 9 ), endometrial ( 6 ) and colon ( 10 ) cancer lines. More recently, telmisartan induced cell cycle arrest in hematologic and non-hematologic malignancies including our study ( 5 , 11 ).…”

Section: Introductionsupporting

confidence: 51%

“…Therefore, repairing cell cycle progression might be an effective strategy for treatment of CCA. In our previous study, telmisartan inhibited human esophageal adenocarcinoma cell proliferation and tumor growth, inducing cell cycle arrest by regulating cell cycle-related molecules ( 11 ). However, the antitumor effect of telmisartan and its mechanism of action in CCA are currently unknown.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Angiotensin receptor blocker telmisartan inhibits cell proliferation and tumor growth of cholangiocarcinoma through cell cycle arrest

Samukawa

Fujihara

Oura

et al. 2017

International Journal of Oncology

Self Cite

View full text Add to dashboard Cite

Cholangiocarcinoma (CCA) is at an advanced stage at the time of its diagnosis, and developing a more effective treatment of CCA would be desirable. Angiotensin II type 1 (AT1) receptor blocker (ARB), telmisartan may inhibit cancer cell proliferation, but the mechanisms by which telmisartan affects various cancers remain unknown. In this study, we evaluated the effects of telmisartan on human CCA cells and to assess the expression of microRNAs (miRNAs). We studied the effects of telmisartan on CCA cells using two cell lines, HuCCT-1 and TFK-1. In our experiments, telmisartan inhibited the proliferation of HuCCT-1 and TFK-1 cells. Additionally, telmisartan induced G0/G1 cell cycle arrest via blockade of the G0 to G1 cell cycle transition. Notably, telmisartan did not induce apoptosis in HuCCT-1 cells. This blockade was accompanied by a strong decrease in cell cycle-related protein, especially G1 cyclin, cyclin D1, and its catalytic subumits, Cdk4 and Cdk6. Telmisartan reduced the phosphorylation of EGFR (p-EGFR) and TIMP-1 by using p-RTK and angiogenesis array. Furthermore, miRNA expression was markedly altered by telmisartan in HuCCT-1. Telmisartan inhibits tumor growth in CCA xenograft model in vivo. In conclusion, telmisartan was shown to inhibit human CCA cell proliferation by inducing cell cycle arrest.

show abstract

Section: Introductionsupporting

confidence: 51%

Section: Introductionmentioning

confidence: 99%

Angiotensin receptor blocker telmisartan inhibits cell proliferation and tumor growth of cholangiocarcinoma through cell cycle arrest

Samukawa

Fujihara

Oura

et al. 2017

International Journal of Oncology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Autophagy plays different roles in the heart during ischemia and reperfusion [2]. The AMP activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) pathway is associated with autophagy [3,4]. Melatonin is the main indoleamine produced by the pineal gland; it is a well-known antioxidant and free radical scavenger [5].…”

Section: Introductionmentioning

confidence: 99%

Melatonin Attenuates Myocardial Ischemia/Reperfusion Injury by Inhibiting Autophagy Via an AMPK/mTOR Signaling Pathway

Chen

Liu

Chen

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Melatonin has been demonstrated to protect cardiac microvascular endothelial cells (CMECs) against ischemia/reperfusion injury (IRI). Autophagy plays different roles in the heart during ischemia and reperfusion. The AMP activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) pathway is associated with autophagy. This study sought to explore whether melatonin regulates CMEC autophagy through the AMPK/mTOR signaling pathway. Methods: The effects of melatonin in IRI were investigated in vivo rat models and in vitro neonatal CMECs. Myocardial infarct size was achieved by Evans blue and triphenyltetrazolium chloride staining. The severity of cell injury was evaluated by cell vitality and lactate dehydrogenase (LDH) release assays, and autophagy was evaluated by transmission electron microscopy and the assessment of autophagy-related gene expression, such as that of Beclin 1 and light chain 3-II. Results: In vivo, melatonin markedly reduced infarcted area, improved cardiac function and decreased LDH release. However, the AMPK activator AICAR and the mTOR inhibitor rapamycin reduced the protective effects of melatonin on IRI. In vitro, Beclin1 and light chain 3-II protein were found to be down-regulated and autophagosomes were found to be reduced in response to melatonin, together with an increase in cell vitality and a decrease in LDH. Treatment with AICAR or rapamycin ablated the benefit observed with melatonin treatment. Conclusions: Melatonin played an important and protective role in CMECs by inhibiting autophagy against IRI via the AMPK/mTOR system.

show abstract

“…Excessive Ang II leads to water-sodium retention, increased intraglomerular pressure, mesangial cells and mesangial matrix increased, causing renal function downregulation. The mechanism is related to the activation of AMPK/mTOR signaling, TLR4/NF-κB signaling and TGF-β signaling [9][10][11].…”

Section: Discussionmentioning

confidence: 99%

RAS Equilibrium Involves in Mesenteric Lymph Return-Mediated Acute Kidney Injury in Mice Underwent Acute Hemorrhage

K¹,

Zhang²,

Xie³

et al. 2020

Preprint

View full text Add to dashboard Cite

Abstract Background: Previous studies demonstrated renin-angiotensin system (RAS) played vital roles in shock-induced organ injury, and mesenteric lymph return was involved in hemorrhagic shock-induced acute kidney injury (AKI). Nevertheless, whether RAS is involved in PHSML-mediated AKI remains unclear. Therefore, this study investigated the role of RAS in post-hemorrhagic shock mesenteric lymph (PHSML)-induced AKI. Methods: After acute hemorrhage and fluid resuscitation, the mice were treated with mesenteric lymph duct ligation (MLDL) and administrations of angiotensin converting enzyme (ACE) inhibitor enalapril, angiotensin (1-7) (Ang (1-7)), angiotensin II (Ang II) type 1 receptor (AT1R) inhibitor losartan, respectively. In addition, the parts of mice with hemorrhage plus MLDL were treated with Ang II, Mas receptor (MasR) inhibitor A-779, respectively. Meanwhile, the ACE2-/- mice received hemorrhage plus MLDL. At 4 h after resuscitation, the kidneys were harvested for the observation of histomorphology and measurement of ACE, ACE2, AT1R, MasR expressions and Ang II and Ang (1-7) levels.Results: Hemorrhagic shock induced renal tissue injury, increased the ACE and AT1R expressions, decreased the ACE2 and MasR expressions in kidney, accompanied by elevated Ang II and depressed Ang (1-7) in kidney. These adverse effects were partially reversed by MLDL or administrations of enalapril, Ang-(1-7), and losartan, respectively. In addition, the beneficial role of MLDL was reversed by ACE2 deficiency and Ang II or A-779 administrations. Conclusion: MLDL alleviates hemorrhagic shock-induced AKI in mice is related to the equilibrium ACE-AngII-AT1R and ACE2-Ang (1-7)-MasR axis.

show abstract

The angiotensin II type 1 receptor antagonist telmisartan inhibits cell proliferation and tumor growth of esophageal adenocarcinoma via the AMPKα/mTOR pathwayin vitroandin vivo

Cited by 40 publications

References 52 publications

Angiotensin receptor blocker telmisartan inhibits cell proliferation and tumor growth of cholangiocarcinoma through cell cycle arrest

Angiotensin receptor blocker telmisartan inhibits cell proliferation and tumor growth of cholangiocarcinoma through cell cycle arrest

Melatonin Attenuates Myocardial Ischemia/Reperfusion Injury by Inhibiting Autophagy Via an AMPK/mTOR Signaling Pathway

RAS Equilibrium Involves in Mesenteric Lymph Return-Mediated Acute Kidney Injury in Mice Underwent Acute Hemorrhage

Contact Info

Product

Resources

About