Perifosine and vitamin D combination induces apoptotic and non-apoptotic cell death in endometrial cancer cells

Endometrial cancer is the most common cancer of the female reproductive system. Combination treatment with specific agents has been widely used as a targeted therapy for cancer. In this study, we aimed to investigate the anti-proliferative and apoptotic effects of varying concentrations of perifosine and vitamin D on the human endometrial cancer cell line (HEC-1A). HEC-1A cells were exposed to perifosine (10 μM, 30 μM), vitamin D (50 nM, 200 nM) and combinations of both for 48 h and 72 h. Monitoring of cell proliferation in a time-dependent manner was performed with the xCELLigence RTCA DP system. The levels of BCL2, BAX and P53 mRNA expression were examined using RT-qPCR. Apoptosis was determined using Annexin V, which were followed by flow cytometry analysis. Ultra-structural morphology of cells was analyzed by transmission electron microscopy (TEM) for 72 h. The anti-proliferative and apoptotic effects of the perifosine+vitamin D combination (30 μM + 200 nM at 48 h and 10 μM + 200 nM at 72 h) on HEC-1A cells were higher than in perifosine and vitamin D alone. It was observed that perifosine has increased the expression of BAX mRNA in HEC-1A cells in a dose-dependent manner. While perifosine+vitamin D combinations increased P53 mRNA expression in HEC-1A cells we did not find any significant change in BCL2, BAX mRNA expression levels. In TEM examinations of HEC-1A cells, perifosine appeared to lead autophagic cell death, whereas vitamin D caused paraptosis-like cell death and combination of perifosine+vitamin D caused apoptotic and non-apoptotic (paraptotic, autophagic and necrotic) cell death. Therefore, it is considered that the combination of both drugs in the treatment of endometrial cancer might be an alternative and effective treatment option through activating the apoptotic and non-apoptotic cell death mechanisms in cancer cells

Anatomic Variations of Paranasal Region in Migraine

Purpose: To assess the incidence of anatomical variations of the paranasal region on computed tomography in migraine patients compared with control subjects

Biochemical, Histopathologic, and Genotoxic Effects of Ethanol Extract of Salvia hypargeia (Fisch. & Mey.) on Incisional and Excisional Wounded Diabetic Rats

Purpose: Nonhealing wounds are a serious problem of diabetic patients. Salvia species are traditionally used for the treatment of wounds. The aim of the study was to investigate the effects of ointment prepared with ethanol extract obtained from the aerial parts of Salvia hypargeia, an endemic plant from Turkey, on diabetic rat incisional and excisional skin wounds. Materials and Methods: Male Wistar albino rats (n: 60) were divided into five groups. Diabetes was induced and two concentrations (0.5% and 1%) of the extract were used for ointments and applied on wounds for 7 and 14 days. Fito cream was chosen as a reference drug. Results: In excisional wounds, healing ratios of 0.5% (63.4% and 99.3%) and 1% (65.5% and 99.9%) S. hypargeia groups were higher compared to control (35.9% and 75.1%), and in incisional wounds, healing ratios of 0.5% (78.1% and 98.5%) and 1% (84.4% and 99.4%) S. hypargeia groups were higher compared to control (30.5% and 72.9%) (p < .01). Hydroxyproline (0.31 +/- 0.3 and 0.34 +/- 0.2) levels were lower and GSH (10.7 +/- 3.1 and 7.6 +/- 0.9) levels were higher in 0.5% and 1% S. hypargeia groups on the 14th day (p < .01). Histopathological results revealed re-epithelialization and formation of granulation tissue in all S. hypargeia groups. Genotoxicologic results indicated, GDI, DCP values, and MN frequency of 0.5% and 1% S. hypargeia groups did not reach to significant levels both on the 7 and 14 days. Conclusions: S. hypargeia may have a potential for therapeutic use in treatment and management of diabetic wounds with a successful topical application