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Background:Quercetin has been shown to induce apoptosis in a number of cancer cell lines, but a quercetin-loaded nanoliposomal formulation with enhanced antitumor activity in C6 glioma cells and its effect on cancer cell death has not been well studied. The aim of this study was to examine if quercetin-loaded liposomes (QUE-NL) has enhanced cytotoxic effects and if such effects involve type III programmed cell death in C6 glioma cells. Methods: C6 glioma cells were treated with QUE-NL and assayed for cell survival, apoptosis, and necrosis. Levels of reactive oxygen species production and loss of mitochondrial membrane potential (∆Ψm) were also determined by flow cytometry assay to assess the effects of QUE-NL. ATP levels and lactate dehydrogenase activity were measured, and Western blotting was used to assay cytochrome C release and caspase expression. Results: QUE-NL induced type III (necrotic) programmed cell death in C6 glioma cells in a dose-dependent and time-dependent manner. High concentrations of QUE-NL induced cell necrosis, which is distinct from apoptosis and autophagy, whereas liposomes administered alone induced neither significant apoptosis nor necrosis in C6 glioma cells. QUE-NL-induced ∆Ψm loss and cytochrome C release had no effect on caspase activation, but decreased ATP levels and increased lactate dehydrogenase activity indicated that QUE-NL stimulated necrotic cell death. Conclusion: C6 glioma cells treated with QUE-NL showed a cellular pattern associated with necrosis without apoptosis and was independent of caspase activity. Nonapoptotic cell death induced by high concentrations of QUE-NL for controlling caspase-independent type III programmed cell death may provide the basis for novel therapeutic approaches to overcome avoidance of apoptosis by malignant cells.

Background/Aims: Although it is widely acknowledged that atherosclerosis is mainly a chronic inflammatory process, in which both miR-29b and interleukin-6 (IL-6) play multifaceted roles, the association between miR-29b and IL-6 remains unknown. The aim of the present study was to explore the relationship between miR-29b and IL-6 and to test whether circulating levels of miR-29b and IL-6 could predict atherosclerosis. Methods: A total of 170 participants were divided into two groups according to carotid intima-media thickness (CIMT): study group (CIMT ≥ 0.9mm) and control group (CIMT < 0.9mm). Levels of circulating miR-29b and IL-6 were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. The association of miR-29b and IL-6 levels with CIMT was assessed using Spearman correlation analysis and multiple linear regression analysis. Results: The study group showed higher miR-29b levels (31.61 ± 3.05 vs. 27.91 ± 1.71 Ct, p < 0.001) and IL-6 levels (3.40 ± 0.67 vs. 2.99 ± 0.37 pg/ml, p < 0.001), compared with the control group. CIMT was positively correlated with miR-29b (r = 0.587, p < 0.001) and IL-6 (r = 0.410, p < 0.001), and miR-29b levels were also correlated with IL-6 (r = 0.242, p = 0.001). Multiple linear regression analysis also showed that CIMT was positively correlated with miR-29b and IL-6. After adjustment for age, body mass index, systolic blood pressure, total cholesterol and C-reactive protein, CIMT was still closely correlated with miR-29b and IL-6. The combination of miR-29b and IL-6 (AUC = 0.901, p < 0.001) offered a better predictive index for atherosclerosis than either miR-29b (AUC = 0.867, p < 0.001) or IL-6 (AUC = 0.747, p < 0.001) alone. Conclusion: Circulating levels of miR-29b and IL-6 may be independently correlated with subclinical atherosclerosis, and may serve as novel biomarkers for the identification of atherosclerosis.