β<sub>2</sub>-adrenergic antagonists suppress pancreatic cancer cell invasion by inhibiting CREB, NF-κB and AP-1

Zhang, Dong; Qing, Yong; Hu, Heng-Tong; Zhang, Min

doi:10.4161/cbt.10.1.11944

Cited by 170 publications

(192 citation statements)

References 28 publications

Supporting

Mentioning

180

Contrasting

Unclassified

Order By: Relevance

“…The effect is cell specific because both ␤ 2 -AR antagonists and agonists have been shown to attenuate cell growth (Carie and Sebti, 2007;Zhang et al, 2010;Toll et al, 2011). In the case of ␤ 2 -AR agonists, the effect seems to be through cAMP-dependent pathways and is subject to antagonism by ICI 118,551 (Carie and Sebti, 2007;Toll et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Cannabinoid Receptor Activation Correlates with the Proapoptotic Action of the β₂-Adrenergic Agonist (R,R′)-4-Methoxy-1-Naphthylfenoterol in HepG2 Hepatocarcinoma Cells

Paul

Ramamoorthy

Scheers

et al. 2012

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Inhibition of cell proliferation by fenoterol and fenoterol derivatives in 1321N1 astrocytoma cells is consistent with ␤ 2 -adrenergic receptor (␤ 2 -AR) stimulation. However, the events that result in fenoterol-mediated control of cell proliferation in other cell types are not clear. Here, we compare the effect of the ␤ 2 -AR agonists (R,RЈ)-fenoterol (Fen) and (R,RЈ)-4-methoxy-1-naphthylfenoterol (MNF) on signaling and cell proliferation in HepG2 hepatocarcinoma cells by using Western blotting and [ 3 H]thymidine incorporation assays. Despite the expression of ␤ 2 -AR, no cAMP accumulation was observed when cells were stimulated with isoproterenol or Fen, although the treatment elicited both mitogen-activated protein kinase and phosphatidylinositol 3-kinase/Akt activation. Unexpectedly, isoproterenol and Fen promoted HepG2 cell growth, but MNF reduced proliferation together with increased apoptosis. The mitogenic responses of Fen were attenuated by 3-(isopropylamino)-1-[(7-methyl-4-indanyl)oxy]butan-2-ol (ICI 118,551), a ␤ 2 -AR antagonist, whereas those of MNF were unaffected. Because of the coexpression of ␤ 2 -AR and cannabinoid receptors (CBRs) and their impact on HepG2 cell proliferation, these G␣ i /G␣ o -linked receptors may be implicated in MNF signaling. Cell treatment with (R)-(ϩ)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-napthalenylmethanone (WIN 55,212-2), a synthetic agonist of CB 1 R and CB 2 R, led to growth inhibition, whereas inverse agonists of these receptors blocked MNF mitogenic responses without affecting Fen signaling. MNF responses were sensitive to pertussis toxin. The ␤ 2 -ARdeficient U87MG cells were refractory to Fen, but responsive to the antiproliferative actions of MNF and WIN 55,212-2. The data indicate that the presence of the naphthyl moiety in MNF results in functional coupling to the CBR pathway, providing one of the first examples of a dually acting ␤ 2 -AR-CBR ligand.

show abstract

Section: Discussionmentioning

confidence: 99%

Cannabinoid Receptor Activation Correlates with the Proapoptotic Action of the β₂-Adrenergic Agonist (R,R′)-4-Methoxy-1-Naphthylfenoterol in HepG2 Hepatocarcinoma Cells

Paul

Ramamoorthy

Scheers

et al. 2012

J Pharmacol Exp Ther

View full text Add to dashboard Cite

show abstract

“…This could affect early metastatic events such as tumor cell invasion, angiogenesis of the primary tumor, cancer cell survival or resistance to chemotherapy, as shown in studies related to other types of solid cancers. 42,43,[69][70][71][72][73][74][75] A stromal-mediated mechanism also implies that other types of metastatic cancers may be influenced by depression, chronic stress and subsequent sympathetic activation. 42,[70][71][72]75 The relative contribution of activation of the HPA axis and adrenal-derived epinephrine (versus nerve-derived NE) to bone remodeling and metastasis remains to be better characterized.…”

Section: Discussionmentioning

confidence: 99%

“…42,43,[69][70][71][72][73][74][75] A stromal-mediated mechanism also implies that other types of metastatic cancers may be influenced by depression, chronic stress and subsequent sympathetic activation. 42,[70][71][72]75 The relative contribution of activation of the HPA axis and adrenal-derived epinephrine (versus nerve-derived NE) to bone remodeling and metastasis remains to be better characterized. As not every breast cancer cell line or tumor biopsy expresses the RANKL receptor (RANK), it will be important to determine whether and how RANK expression/signaling is regulated in cancer cells at the various stages of the metastatic process and to investigate the possible existence of additional mechanisms by which sympathetic activation may stimulate tumor metastasis.…”

Section: Discussionmentioning

confidence: 99%

Chronic stress, sympathetic activation and skeletal metastasis of breast cancer cells

Elefteriou¹

2015

BoneKEy Reports

View full text Add to dashboard Cite

Improved detection programs and new therapies significantly improved the 5-year survival rate of women with breast cancer. However, some women still relapse and succumb to cancer because of metastatic disease. In particular, chronically depressed patients do not seem to benefit from newly developed treatments and present with shorter survival. The reason for this association is unclear, but recent cues from preclinical studies point to the possible contribution of neuroendocrine factors generated in response to chronic stress and depression. Retrospective clinical studies also suggest a beneficial effect of sympathetic blockade in terms of less advanced disease at diagnosis, lower cancer-specific mortality, longer disease-free survival and reduced metastasis development and tumor recurrence, especially in patients who have taken propranolol before diagnosis. Therefore, b-blockers or therapies normalizing sympathetic tone might be beneficial as early adjuvant therapies to limit skeletal metastases and growth and eventually to improve prognosis in patients with breast cancers.

show abstract

“…These effects, requiring cellular uptake of the drug, are not mediated by the b-adrenoreceptors, and are not shared by most other b-blockers (17)(18)(19). In experimental models, propranolol administration was shown to prevent or reduce cancer progression, by inhibiting cAMP-responsive element-binding protein (CREB), NF-kB, and activator protein (AP-1), inducting apoptosis, or reducing matrix metalloproteinase (MMP)-9 activation and tumor angiogenesis (20)(21)(22)(23). In humans, propranolol was recently reported to control the growth of proliferative infantile hemangioma (24).…”

Section: Introductionmentioning

confidence: 99%

Effect of Long-term Propranolol Treatment on Hepatocellular Carcinoma Incidence in Patients with HCV-Associated Cirrhosis

N’Kontchou

Aout

Mahmoudi

et al. 2012

Cancer Prevention Research

View full text Add to dashboard Cite

Propranolol bears antioxidant, anti-inflammatory, and antiangiogenic properties and antitumoral effects and therefore is potentially active in the prevention of hepatocellular carcinoma (HCC). We retrospectively assessed the impact of propranolol treatment on HCC occurrence in a cohort of 291 patients with compensated viral C (HCV) cirrhosis, prospectively followed and screened for HCC detection.Of ; platelet count, 137 AE 59 Giga/L) did not. Among patients with OV, 50 received treatment by propranolol. During a median follow-up of 54 months interquartile range (32-82), 61 patients developed an HCC. The 3-and 5-year HCC incidence was 4% and 4%, and 10% and 20% for patients treated and not treated by propranolol, respectively (Gray test, P ¼ 0.03). In multivariate analysis, propranolol treatment was associated with a decrease risk of HCC occurrence [HR, 0.25; 95% confidence interval (CI), 0.09-0.65; P ¼ 0.004], and was the only independent predictive factor of HCC occurrence in patients with OV (HR, 0.16; CI, 0.06-0.45; P ¼ 0.0005). The benefit of propranolol was further supported by propensity scores analyses.Conclusion: This retrospective long-term observational study suggests that propranolol treatment may decrease HCC occurrence in patients with HCV cirrhosis. These findings need to be verified by prospective clinical trial. Cancer Prev Res; 5(8);

show abstract

β₂-adrenergic antagonists suppress pancreatic cancer cell invasion by inhibiting CREB, NF-κB and AP-1

Cited by 170 publications

References 28 publications

Cannabinoid Receptor Activation Correlates with the Proapoptotic Action of the β₂-Adrenergic Agonist (R,R′)-4-Methoxy-1-Naphthylfenoterol in HepG2 Hepatocarcinoma Cells

Cannabinoid Receptor Activation Correlates with the Proapoptotic Action of the β₂-Adrenergic Agonist (R,R′)-4-Methoxy-1-Naphthylfenoterol in HepG2 Hepatocarcinoma Cells

Chronic stress, sympathetic activation and skeletal metastasis of breast cancer cells

Effect of Long-term Propranolol Treatment on Hepatocellular Carcinoma Incidence in Patients with HCV-Associated Cirrhosis

Contact Info

Product

Resources

About

β2-adrenergic antagonists suppress pancreatic cancer cell invasion by inhibiting CREB, NF-κB and AP-1

Cited by 170 publications

References 28 publications

Cannabinoid Receptor Activation Correlates with the Proapoptotic Action of the β2-Adrenergic Agonist (R,R′)-4-Methoxy-1-Naphthylfenoterol in HepG2 Hepatocarcinoma Cells

Cannabinoid Receptor Activation Correlates with the Proapoptotic Action of the β2-Adrenergic Agonist (R,R′)-4-Methoxy-1-Naphthylfenoterol in HepG2 Hepatocarcinoma Cells

Chronic stress, sympathetic activation and skeletal metastasis of breast cancer cells

Effect of Long-term Propranolol Treatment on Hepatocellular Carcinoma Incidence in Patients with HCV-Associated Cirrhosis

Contact Info

Product

Resources

About

β₂-adrenergic antagonists suppress pancreatic cancer cell invasion by inhibiting CREB, NF-κB and AP-1

Cannabinoid Receptor Activation Correlates with the Proapoptotic Action of the β₂-Adrenergic Agonist (R,R′)-4-Methoxy-1-Naphthylfenoterol in HepG2 Hepatocarcinoma Cells

Cannabinoid Receptor Activation Correlates with the Proapoptotic Action of the β₂-Adrenergic Agonist (R,R′)-4-Methoxy-1-Naphthylfenoterol in HepG2 Hepatocarcinoma Cells