BackgroundGlioblastoma (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.MethodsMonolayer and spheroid cultures of T98G human GBM cell line were used to evaluate the effects of IM (10 μM), Nos (10 μM) and their combination on cell proliferation and apoptotic indexes, cell cycle, the levels of antiapoptotic MK, MRP-1, p170, PFGFR-α, EGFR, bcl-2 proteins, apoptotic caspase-3 levels, morphology (SEM) and ultrastructure (TEM) for 72 hrs. Results were statistically analyzed using the Student's t-test.ResultsThe combination group induced highest decrease in cell proliferation and apoptotic indexes, caspase-3 levels, MRP-1 and PDGFR-α levels. The decrease in p170 levels were lower than IM but higher that NOS. The highest increases were in EGFR, MK, bcl-2 and cAMP levels in the combination group. The G0+G1 cell cycle arrest at the end of 72nd hr was the lowest in the combination group. Apoptotic appearence was observed rarely both in the morphologic and ultrastructural evaluation of the combination group. In addition, autophagic vacuoles which were frequently observed in the IM group were observed rarely.ConclusionsThe combination of Nos with IM showed antagonist effect in T98G human GBM cells in vitro. This antagonist effect was correlated highly with MK levels. The effects of NOS on MRP-1, MK and receptor tyrosine kinase levels were firstly demonstrated in our report. In addition, we proposed that MK is one of the modulator in the switch of autophagy to cell death or survival/resistance.

Our results show that PON-1 activity is lower in patients with FMF. Reduced PON-1 activity and increased MPV, independent of the oxidative stress status of these patients, may lead to increased atherosclerotic propensity in FMF.

ObjectiveThe aim of the study was to investigate whether lithium chloride and medroxyprogesterone acetate can potentiate the cytotoxicity of imatinib mesylate in human endometrial cancer in vitro and the effect of midkine in these therapies.MethodsImatinib mesylate (50 µM), lithium chloride (100 µM), medroxyprogesterone acetate (200 µM) and their combination were applied to monolayer and three dimensional cultures of human Ishikawa endometrial cancer for 72 hours. The cell proliferation index, apoptotic index, caspase-3 and midkine levels, cell cycle distributions in monolayer cultures and cell ultrastructure in spheroid cultures were evaluated. Results were statistically analyzed using the Student's t-test.ResultsAll drug applications inhibited cell proliferation (p<0.05), however the combination were the effective groups for 72 hours (p<0.05). Interestingly, although the loss of efficiency was seen higly seen every 24 hours at single applications, the inhibition rates of the combination groups were almost same for 72 hours. In concordance with these results, the apoptotic index, caspase-3 levels (p<0.05), cell morphology and ultrastructure damages were much higher in the combination groups. Imatinib mesylate induced S-phase arrest, however other groups induced G0+G1-phase arrest at 24 hours and all groups induced G0+G1 arrest at 72 hours (p<0.05). Imatinib mesylate and imatinib mesylate with medroxyprogesterone acetate induced highest decrease in midkine levels, respectively (p<0.05).ConclusionThe present study showed that the combination of imatinib mesylate with lithium chloride and medroxyprogesterone acetate is highly active in Ishikawa endometrial carcinoma in vitro and the inhibition of midkine involved in their mechanism of action against endometrium defense.

Type 2 diabetes mellitus (DM) affects a large population worldwide. DM is often considered as a syndrome of disordered glucose metabolism. Current conventional drug therapies for DM are usually insufficient and medicinal herbs with antihyperglycemic activities are increasingly sought by diabetic patients and health care professionals. Nerium Oleander (N.O.) is known to be effective in lowering of postprandial blood glucose in DM patients as a folk remedy. In this study we aimed to evaluate effect of N.O. distillate in glucose uptake activity of hepatocytes and adipocytes. The human hepatoma cells Hep3B and mouse adipocyte 3T3-L1 cells were cultured. Depending on the groups, different concentrations insulin (1, 10, 20 IU/ml) and N.O. (0.1, 1, 10, 50 µg/ml) were added to medium for 48 h. Cellular toxicity and proliferation were evaluated by LDH secretion levels and MTT test. A metabolizable fluorescent derivative of glucose, 2-NBDG and FITC-insulin were used for glucose uptake and insulin binding activity. Insulin increased cellular proliferation and decreased LDH leakage and apoptosis in both cell types. Lower dosages of N.O. has no significant effect on apoptosis and cell number while at the highest dosages minimal cytotoxicity was seen mainly in adipocytes. Main effect of N.O. treatment was increased glucose uptake in Hep3B and 3T3-L1 cells (P<0.001). Our results showed that N.O. may be offered as new approaches to treatment of type 2 diabetes by modulating cellular glucose uptake.

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