3-Hydroxy-3',4'-dimethoxyflavone suppresses Bcl-w-induced invasive potentials and stemness in glioblastoma multiforme.

3-Hydroxy-3',4'-dimethoxyflavone (HDMF) is a natural chemical product that is not currently regarded as a drug. In our study, we employed glioblastoma cells and cell biology and biochemistry approaches to investigate the potential of HDMF as a natural anticancer therapy option. FACS analysis showed that treatment concentration of HDMF does not exert cytotoxicity on U251 cells. Wound-healing and invasion assays showed that HDMF dose-dependently decreased the migratory and invasive potentials of these cells, likely by indirectly inhibiting MMP-3 activity as a result of the inhibition of p38 and ERK signaling proteins - an effect of HDMF also shown by Western blotting. HDMF inhibits Bcl-w-induced neurosphere formation and the expression of glioma stem cell markers, such as Musashi, Sox-2 and c-myc. These results indicate that HDMF suppresses migratory or invasive potentials and stemness and functions as a negative agent against the aggressiveness of glioblastoma cells. We propose that HDMF has potential as anticancer drug for inhibiting the aggressiveness of glioblastoma multiforme (GBM).

Association of optimal blood pressure with mortality in patients taking antihypertensive medications.

We investigated the relationship between blood pressure (BP) and mortality in patients taking antihypertensive medications in the Korean using data from the 2007-2015 Korean National Health and Nutrition Examination Surveys. A total of 6601 patients aged 30-74 years were included. Systolic BP (SBP) and diastolic BP (DBP) were both divided into four groups as follows: SBP < 120, 120 ≤ SBP ≤ 129 130 ≤ SBP ≤ 139, and SBP ≥ 140; DBP < 70, 70 ≤ DBP ≤ 79, 80 ≤ DBP ≤ 89, and DBP ≥ 90. The survival rates and hazard ratios were evaluated using Kaplan-Meier curves and multivariable Cox regression analyses. To evaluate the predictability of all-cause mortality according to SBP and/or DBP, we calculated Harrell's concordance-index. The lowest DBP group had a high risk of mortality regardless of the SBP status. The group with DBP < 70 mm Hg and SBP ≥ 140 mm Hg showed the highest mortality. The discriminatory ability calculated using Harrell's C-indexes was greater for the combination of SBP and DBP compared to DBP or SBP alone. These results suggest that it is more effective to simultaneously evaluate the effect of SBP and DBP to predict mortality; clinicians should manage DBP < 70 mm Hg when treating hypertensive patients.

Specificity protein 1 expression contributes to Bcl-w-induced aggressiveness in glioblastoma multiforme.

We already had reported that Bcl-w promotes invasion or migration in gastric cancer cells and glioblastoma multiforme (GBM) by activating matrix metalloproteinase-2 (MMP-2) via specificity protein 1 (Sp1) or ß-cateinin, respectively. High expression of Bcl-w also has been reported in GBM which is the most common malignant brain tumor and exhibits aggressive and invasive behavior. These reports propose that Bcl-w-induced signaling is strongly associated with aggressive characteristic of GBM. We demonstrated that Sp1 protein or mRNA expression is induced by Bcl-w using Western blotting or RT-PCR, respectively, and markedly elevated in high-grade glioma specimens compared with low-grade glioma tissues using tissue array. However, relationship between Bcl-w-related signaling and aggressive characteristic of GBM is poorly characterized. This study suggested that Bcl-w-induced Sp1 activation promoted expression of glioma stem-like cell markers, such as Musashi, Nanog, Oct4 and sox-2, as well as neurosphere formation and invasiveness, using western blotting, neurosphere formation assay, or invasion assay, culminating in their aggressive behavior. Therefore, Bcl-w-induced Sp1 activation is proposed as a putative marker for aggressiveness of GBM.