The purpose of the study was to investigate whether carvedilol has an antiproliferative effect alone and whether carvedilol provides an additive, synergistic or antagonistic effect on imatinib mesylate-induced cytotoxicity in both C6 glioma monolayer and spheroid culture. The C6 rat glioma chemoresistant experimental brain tumour cell line, that is notoriously difficult to treat with combination chemotherapy, was used both in monolayer and spheroid cultures. We treated C6 glioma cells with carvedilol alone and a combination of carvedilol and imatinib mesylate at a concentration of 10 microM. Following treatment, we evaluated cell proliferation index, bromodeoxyuridine labelling index (BrDU-LI), cell cycle distributions, apoptotic cell percentages, cAMP levels and three dimensional cell morphology at monolayer cultures. In addition BrDU-LI, volume and morphology of spheroids were also assessed. Carvedilol and imatinib mesylate alone reduced cell number, BrDU-LI, cAMP levels and spheroid volume. Carvedilol and imatinib mesylate arrested cells at G0/G1 phase in a time-dependent manner and time-independent manner, respectively. Carvedilol increased apoptosis rate only at the 24th h, but imatinib mesylate did for all time intervals. Interestingly carvedilol, drug with well-known protective effect on mitochondria, induced severe mitochondria damage, and imatinib mesylate induced autophagy confirmed only by transmission electron microscopy. These results suggest that carvedilol showed antitumour activity against rat C6 glioma cells and a combination of carvedilol with imatinib mesylate resulted in enhanced in vitro antitumour activity.

Glioblastoma (GBM) develops resistance to the advances in chemotherapy leading to poor prognosis and life quality. Consequently, new treatment modalities are needed. Our aims were to investigate the effects of combined noscapine (NOS) and imatinib mesylate (IM) on human GBM in vitro and the role of midkine (MK) in this new combination treatment.

Bilir A, et al. J Gynecol Oncol. 2011 Dec;22(4):225-232. http://dx.doi.org/10.3802/jgo.2011.22.4.225

Background: 1,25-Dihydroxyvitamin D₃ (1,25-OH D₃) plays an important role in mineralized tissue metabolism, including teeth. However, few studies have addressed its role in odontoblastic differentiation of human dental pulp-stem cells (hDPSCs). Aim: This study aimed to understand the influence of various concentrations of 1,25-OH D₃ on the proliferation capacity and early dentinogenesis responses of hDPSCs. Materials and Methods: hDPSCs were obtained from the impacted third molar teeth. Monolayer cultured cells were incubated with a differentiation medium containing different concentrations of 1,25-OH D₃ (0.001, 0.01, and 0.1 µM). All groups were evaluated by S-phase rate [immunohistochemical (IHC) bromodeoxyuridine (BrdU) staining], STRO-1 and dentin sialoprotein (DSP)+ levels (IHC), and alkaline phosphatase (ALP, enzyme-linked immunosorbent assay (ELISA)) levels. Results: The number of cells that entered the S-phase was determined to be the highest and lowest in the control and 0.001 µM 1,25-OH D₃ groups, respectively. The 0.1 µM vitamin D₃ group had the highest increase in DSP+ levels. The highest Stro-1 levels were detected in the control and 0.1 µM 1,25-OH D₃ groups, respectively. The 0.1 µM 1,25-OH D₃ induced a mild increase in ALP activity. Conclusions: This study demonstrated that 1,25-OH D₃ stimulated odontoblastic differentiation of hDPSCs in vitro in a dose-dependent manner. The high DSP + cell number and a mild increase in ALP activity suggest that DPSCs treated with 0.1 μM 1,25-OH D₃ are in the later stage of odontoblastic differentiation. The results confirm that 1,25-OH D₃-added cocktail medium provides a sufficient microenvironment for the odontoblastic differentiation of hDPSCs in vitro.

The chemical compositions of the water-distilled essential oil of Stachys cretica ssp. lesbiaca Rech. fil. and S. cretica ssp. trapezuntica Rech. fil. were determined by GC and GC–MS. Altogether 63 compounds were identified. The sesquiterpene hydrocarbon, germacrene D (20.3% and 12.9% respectively) was the main component identified in both oils. Furthermore, ethanol, light petroleum, dichloromethane, ethyl acetate and n-butanol extracts prepared from the aerial parts of the plants were tested for their antimicrobial activities against six bacterial strains and the yeast Candida albicans. The extracts exhibited no antibacterial activity, but the light petroleum and n-butanolic fractions showed low antifungal activities. Crude ethanolic extracts of the two subspecies were tested for their ability to inhibit the growth of HL-60 and Ishikawa human tumor cell lines. The IC₅₀ values were 100 μg/mL for the HL-60 cell line and 200 μg/mL for the Ishikawa cell line.