Cyclophosphamide stimulates endoplasmic reticulum stress and induces apoptotic cell death in human glioblastoma cell lines.

Cyclophosphamide (CP) is an alkylating chemotherapeutic agent commonly used in cancer treatments. In this study, we aimed to investigate the effects of 4-Hydroperoxy cyclophosphamide (4-HC), which is active form of CP, on glucose-regulated protein 78 (GRP78), activating transcription factor 6 (ATF6), phospho-protein kinase R (PKR)-like endoplasmic reticulum (ER) kinase (p-PERK), phospho-inositol-requiring enzyme 1 alpha (p-IRE1α), eukaryotic translation initiation factor 2 alpha (eIF2α), and caspase-3 messenger ribonucleic acids (mRNAs) and proteins that play roles in the ER stress pathway and apoptosis in U87 and T98 human glioblastoma cell lines. U87 and T98 human glioblastoma cell lines were divided into control and 4-HC-treated groups. Cell viability assay was used to detect the half maximal inhibitory concentration (IC50) for 24 hours of 4-HC. Immunocytochemistry and quantitative polymerase chain reaction (qPCR) methods were used to evaluate the levels of proteins and their mRNAs. The IC50 values of U87 and T98 cells were calculated as 15.67±0.58 µM and 19.92±1 µM, respectively. The levels of GRP78, ATF6, p-PERK, p-IRE1α, eIF2α, and caspase-3 protein expressions in the 4-HC-treated group compared to that in the control group. These increased protein expressions also were correlated with the mRNA levels. The ER stress signal pathway could be active in 4-HC-induced cell death. Further studies of ER-related stress mechanisms in anticancer treatment would be important for effective therapeutic strategies.

Evaluation of the protective effects of non-thermal atmospheric plasma on alveolar bone loss in experimental periodontitis.

OBJECTIVES: The inhibition of bone destruction is one of the main goals of periodontitis treatment. The aim of this study was to investigate the protective effects of non-thermal atmospheric plasma (NTAP) on alveolar bone loss radiographically, histomorphometrically, and histologically in experimental periodontitis in rats. MATERIALS AND METHODS: A total of twenty-eight rats were randomly divided into three groups: control group (CG) (n = 8), periodontitis group (PG) (n = 10), and NTAP group (NTAPG) (n = 10). In PG and NTAPG, experimental periodontitis was created with ligating. The kINPen 11 plasma jet was applied around the ligatured teeth in NTAPG. The samples from each group were radiographically assessed with microcomputed tomography (micro-CT); then, histological (presence of osteoclasts and inflammatory cells) and immunohistochemical (immunoreactive of OCN and ALP) findings were compared. RESULTS: The results revealed a significant increase in alveolar bone loss in the PG compared with CG and NTAPG (p < 0.05). Inflammation, alveolar resorption, and cement damage were reduced significantly in the group treated with NTAP compared to the PG (p < 0.05). Significantly higher levels of osteoclasts were detected in the PG in comparison with both CG and NTAPG (p < 0.05). The lowest osteocalcin and ALP values were determined in PG, and the differences between PG and both groups were also significant (p < 0.05). CONCLUSION: Within the limitations of the present study, we can say that NTAP may enhance the bone remodeling process by inhibiting inflammation and preventing alveolar bone destruction. CLINICAL RELEVANCE: NTAP has clinical potential for accelerating and treating periodontitis with the inflammatory response modulation, osteoblast differentiation, and alveolar bone loss reduction.