PPARγ ligands suppress the feedback loop between E2F2 and cyclin-E1

Komatsu, Yôko; Ito, Ichiaki; Wayama, Mitsutoshi; Fujimura, Akiko; Akaogi, Kensuke; Machida, Hikaru; Nakajima, Yuka; Kuroda, Takeshi; Ohmori, Kazuji; Murayama, Akiko; Kimura, Kazuhiro; Yanagisawa, Junn

doi:10.1016/j.bbrc.2008.03.046

Cited by 6 publications

(7 citation statements)

References 13 publications

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“…Other PPAR-γ partial agonists also inhibit cancer cell proliferation by inducing cell cycle arrest [16–18]. Troglitazone, which is a strong activator of PPAR-γ, was previously reported to inhibit the mRNA levels of cyclin E and E2F2 in a colon cancer cell line [16]. In this study, no significant reduction in E2F2 was identified following telmisartan treatment, although telmisartan significantly decreased cyclin E expression.…”

Section: Discussionmentioning

confidence: 52%

“…The protein levels of p21 Cip1 also increased in response to telmisartan treatment (Figure 2D). PPAR-γ ligands were previously reported to inhibit the mRNA expressions of cyclin E and E2F2 in a colon cancer cell line [16]. However, E2F2 expression in EAC cells was not detected following treatment with telmisartan (Figure 2C).…”

Section: Resultsmentioning

confidence: 87%

“…Telmisartan is the strongest PPAR-γ partial agonist among the ARBs (irbesartan, candesartan, valsartan) [14]. Other PPAR-γ partial agonists also inhibit cancer cell proliferation by inducing cell cycle arrest [16–18]. Troglitazone, which is a strong activator of PPAR-γ, was previously reported to inhibit the mRNA levels of cyclin E and E2F2 in a colon cancer cell line [16].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2016

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Telmisartan, a widely used antihypertensive drug, is an angiotensin II type 1 (AT1) receptor blocker (ARB). This drug inhibits cancer cell proliferation, but the underlying mechanisms in various cancers, including esophageal cancer, remain unknown. The aim of the present study was to evaluate the effects of telmisartan on human esophageal cancer cell proliferation in vitro and in vivo. We assessed the effects of telmisartan on human esophageal adenocarcinoma (EAC) cells using the cell lines OE19, OE33, and SKGT-4. Telmisartan inhibited the proliferation of these three cell lines via blockade of the G0 to G1 cell cycle transition. This blockade was accompanied by a strong decrease in cyclin D1, cyclin E, and other cell cycle-related proteins. Notably, the AMP-activated protein kinase (AMPK) pathway, a fuel sensor signaling pathway, was enhanced by telmisartan. Compound C, which inhibits the two catalytic subunits of AMPK, enhanced the expression of cyclin E, leading to G0/G1 arrest in human EAC cells. In addition, telmisartan reduced the phosphorylation of epidermal growth factor receptor (p-EGFR) and ERBB2 in vitro. In our in vivo study, intraperitoneal injection of telmisartan led to a 73.2% reduction in tumor growth in mice bearing xenografts derived from OE19 cells. Furthermore, miRNA expression was significantly altered by telmisartan in vitro and in vivo. In conclusion, telmisartan suppressed human EAC cell proliferation and tumor growth by inducing cell cycle arrest via the AMPK/mTOR pathway.

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Section: Discussionmentioning

confidence: 52%

Section: Resultsmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

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

et al. 2016

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“…By upregulation of CDK inhibitors, PPARγ agonists therefore induce arrest of the cell cycle. In addition, thioglitazone also suppresses the feedback loop containing E2F, cyclin E1, and Rb protein [56] . It is noteworthy that PPARγ ligand-mediated cell cycle arrest is cell specific, and variations in responses exist among different cancer cell lines [43] .…”

Section: Inhibition Of Cellular Proliferationmentioning

confidence: 99%

Peroxisome proliferator-activated receptor γ and colorectal cancer

Dai

Wang²

2010

WJGO

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Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily and ligand-activated transcription factors. PPARγ plays an important role in adipocyte differentiation, lipid storage and energy dissipation in adipose tissue, and is involved in the control of inflammatory reactions as well as in glucose metabolism through the improvement of insulin sensitivity. Growing evidence has demonstrated that activation of PPARγ has an antineoplastic effect in tumors, including colorectal cancer. High expression of PPARγ is detected in human colon cancer cell lines and adenocarcinoma. This review describes the molecular mechanisms by which PPARγ regulates tumorigenesis in colorectal cancer, and examines current clinical trials evaluating PPARγ agonists as therapeutic agents for colorectal cancer.

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“…Although many recent studies have associated E2F2 activity with inappropriate cell proliferation and/or apoptosis in various tumor types [4–6], the role of E2F2 in NPC remains unknown. Several research groups have identified E2F2 as a mediator in the ability of peroxisome proliferator-activated receptors (PPARs) α , β , and γ to regulate cell proliferation [7–9]. PPAR- γ is expressed strongly in adipose tissue and has been shown to play a key role in the onset of obesity [10], T2DM [11], metabolic syndrome [12], and cardiovascular disease [13], and the activated form plays an inhibitory role in cell growth and proliferation [14].…”

Section: Introductionmentioning

confidence: 99%

PPAR-γLigand Inhibits Nasopharyngeal Carcinoma Cell Proliferation and Metastasis by Regulating E2F2

et al. 2019

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Purpose. Peroxisome proliferator-activated receptor-γ (PPAR-γ) is a nuclear hormone receptor with a key role in lipid metabolism. Previous studies have identified various roles of PPAR-γ in cell cycle progression, cellular proliferation, and tumor progression. However, no report has described a role for PPAR-γ in human nasopharyngeal carcinoma (NPC). Notably, some studies have reported a relationship between PPAR-γ and E2F transcription factor 2 (E2F2), which has been identified as a regulator of cell cycle, apoptosis, and the DNA damage response. Notably, E2F2 has also been reported to correlate with a poor prognosis in patients with various malignancies. Methods. We used immunohistochemical (IHC) and western blot methods to evaluate PPAR-γ and E2F2 expression and function in nonkeratinizing NPC and nasopharyngitis (NPG) tissue samples, as well as western blotting and CCK8 analyses in the NPC cell lines, CNE1 and CNE2. Results. We observed lower levels of PPAR-γ expression in nonkeratinizing NPC tissues compared with NPG tissues and determined an association between a low level of PPAR-γ expression with a more advanced tumor stage. Furthermore, strong E2F2 expression was detected in nonkeratinizing NPC tissues. We further demonstrated that rosiglitazone, a PPAR-γ agonist, reduced E2F2 expression and proliferation in NPC cell lines. Conclusions. Our study results revealed a novel role for the PPAR-γ–E2F2 pathway in controlling NPC cell proliferation and metastasis.

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PPARγ ligands suppress the feedback loop between E2F2 and cyclin-E1

Cited by 6 publications

References 13 publications

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

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

Peroxisome proliferator-activated receptor γ and colorectal cancer

PPAR-γLigand Inhibits Nasopharyngeal Carcinoma Cell Proliferation and Metastasis by Regulating E2F2

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