Wogonoside exerts potential anti-tumor activity against bladder cancer in vivo and in vitro via regulation of GSK3β/ERK/AKT signaling pathway

Purpose: To explore the antitumor activity of wogonoside on bladder cancer, and its underlying mechanism of action. Methods: Methyl thiazolyl tetrazolium (MTT) assay was applied to evaluate the anti-proliferative activity of wogonoside (2 - 128 μM) against bladder cancer 5637 cell line at different times, and the half maximal inhibitory concentration (IC50) was measured. The antitumor activity of wogonoside (30 mg/kg, i.p.) against bladder cancer 5637 cell line was confirmed via in vivo experiments on nude mice bearing human bladder cancer 5637 cells. Additionally, western blotting assay and enzyme-linked immunosorbent assay (ELISA) were used to investigate expression levels of caspase-3, caspase-9, B cell lymphoma/leukemia-2 (Bcl-2), Bcl-2 associated X protein (Bax), phosphorylated (p)-glycogen synthase kinase (GSK)-3β, p-extracellular signal-regulated kinases (p-ERK), and p-(protein kinase B) AKT. Results: The in vitro results reveal that wogonoside has remarkable anti-proliferative activity against bladder cancer 5637 cells with IC50 of 20.59 μM, in a concentration-and time-dependent manner. Furthermore, wogonoside treatment also suppressed tumor volume of nude mice bearing bladder cancer 5637 cell (p < 0.01). The potential mechanisms seems to be mainly associated with apoptosis mediated by mitochondria via up-regulation of caspase-3, caspase-9, and Bax levels, and downregulation of Bcl-2, p-GSK-3β, p-ERK, and p-AKT. Conclusion: The results reveal that wogonoside possesses anti-tumor potentials against bladder cancer. Further translational studies are warranted to test the clinical application of this medicinal agent in bladder cancer

Baicalein and U0126 suppress bladder cancer proliferation via MAPK signaling pathway

Purpose: To investigate baicalein and 1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio] butadiene (U0126)effects on human bladder cell line T24 proliferation and related mechanisms.Methods: Twenty micromoles of baicalein or 10 μM U0126 were incubated with T24 cells. Cell viability was tested by CCK8 assay. Cell cycle was evaluated by flow cytometry while cell apoptosis was detected by Annexin V/PI and TUNEL assay. MAPK signaling pathway was evaluated by real time polymerase chain reaction (RT-PCR) and western blot.Results: Baicalein and U0126 suppressed bladder cancer cell T24 proliferation by blocking cell cycle in G0~G1 phase. TUNEL and Annexin V/PI detection showed both baicalein and U0126 induced T24 cell apoptosis. Baicalein and U0126 significantly down-regulated MAPK signaling pathway related molecule activity in both mRNA and protein levels (p < 0.05).Conclusion: Baicalein and U0126 restrain bladder cancer cell proliferation and promote cell apoptosis by affecting MAPK signaling pathway. Thus, they have  potentials for use in the treatment of bladder cancer.Keywords: Bladder cancer, Baicalein, 1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio] butadiene, MAPK signal pathway, Apoptosi

Wogonoside exerts potential anti-tumor activity against bladder cancer in vivo and in vitro via regulation of GSK3β/ERK/AKT signaling pathway

Purpose: To explore the antitumor activity of wogonoside on bladder cancer, and its underlying mechanism of action. Methods: Methyl thiazolyl tetrazolium (MTT) assay was applied to determine the anti-proliferative activity of wogonoside (2 - 128 μM) on bladder cancer 5637 cell line at various times, and the halfmaximal inhibitory concentration (IC50) was measured. The antitumor activity of wogonoside (30 mg/kg, ip) against bladder cancer 5637 cell line was evaluated in nude mice bearing human bladder cancer 5637 cells. Additionally, western blotting and enzyme-linked immunosorbent assay (ELISA) were carried out to investigate the levels of the caspase-3, caspase-9, B cell lymphoma/leukemia-2 (Bcl-2), Bcl-2 associated X-protein (Bax), phosphorylated (p)-glycogen synthase kinase (GSK)-3β, p-extracellular signal-regulated kinases (p-ERK), and p-(protein kinase B) AKT. Results: The in vitro results revealed that wogonoside exerted anti-proliferative activity against bladder cancer 5637 cells with an IC50 of 20.59 μM (p < 0.01), in a concentration- and time-dependent manner. Furthermore, wogonoside treatment also significantly suppressed tumor volume in mice (p < 0.01). The potential mechanisms were mainly associated with apoptosis mediated by mitochondria via upregulation of caspase-3, caspase-9, and Bax levels and down-regulation of Bcl-2, p-GSK-3β, p-ERK, and p-AKT. Conclusion: The results reveal that wogonoside has remarkable anti-tumor potentials against bladder cancer. Further translational studies are warranted to test the clinical application of this medicinal agent in bladder cancer

Trends in Prehypertension and Hypertension Risk Factors in US Adults: 1999-2012.

Prehypertension is associated with increased risk for hypertension and cardiovascular disease. Data are limited on the temporal changes in the prevalence of prehypertension and risk factors for hypertension and cardiovascular disease among US adults with prehypertension. We analyzed data from 30 958 US adults ≥20 years of age who participated in the National Health and Nutrition Examination Surveys between 1999 and 2012. Using the mean of 3 blood pressure (BP) measurements from a study examination, prehypertension was defined as systolic BP of 120 to 139 mm Hg and diastolic BP <90 mm Hg or diastolic BP of 80 to 89 mm Hg and systolic BP <140 mm Hg among participants not taking antihypertensive medication. Between 1999-2000 and 2011-2012, the percentage of US adults with prehypertension decreased from 31.2% to 28.2% (P trend=0.007). During this time period, the prevalence of several risk factors for cardiovascular disease and incident hypertension increased among US adults with prehypertension, including prediabetes (9.6% to 21.6%), diabetes mellitus (6.0% to 8.5%), overweight (33.5% to 37.3%), and obesity (30.6% to 35.2%). There was a nonstatistically significant increase in no weekly leisure-time physical activity (40.0% to 43.9%). Also, the prevalence of adhering to the Dietary Approaches to Stop Hypertension eating pattern decreased (18.4% to 11.9%). In contrast, there was a nonstatistically significant decline in current smoking (25.9% to 23.2%). In conclusion, the prevalence of prehypertension has decreased modestly since 1999-2000. Population-level approaches directed at adults with prehypertension are needed to improve risk factors to prevent hypertension and cardiovascular disease

Hypertension in African Americans Aged 60 to 79 Years: Statement From the International Society of Hypertension in Blacks

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111078/1/jch12511.pd