Pitavastatin induces caspase-mediated apoptotic death through oxidative stress and DNA damage in combined with cisplatin in human cervical cancer cell line.

Pitavastatin (PITA) is a 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitor to treat hypercholesterolemia and in recent studies is focused that its potential anti-cancer effect. This study was aimed to elucidate the effect of PITA alone and in combination with cisplatin on cervical cancer cells (HeLa) in vitro. Cytotoxicity of PITA (5-200 µM) was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and neutral red uptake (NRU) assays for 24, 48, and 72 h. Cell apoptosis and cell cycle analyses were performed in flow cytometry (0.1-100 µM). The evaluation of genotoxic effects and oxidative DNA damage of PITA (2-200 µM) were performed with standard comet assay, formamidopyrimidine glycosylase (fpg)-modified comet assay, and reactive oxygen species (ROS) activation in HeLa cells. PITA alone reduced cell viability in a dose-dependent manner (20-200, 20-200, and 5-200 µM for 24, 48, and 72 h, respectively, in MTT). The combined treatment of PITA with cisplatin resulted in significantly greater inhibition of cell viability. ROS and DNA damage increased significantly at 100 µM for 4 h and 20 µM for 24 h, respectively. PITA-induced apoptosis, an increased proportion of sub G1 cells, was monitored, and also, it increased the expression of active caspase-9 and caspase-3 and upregulated cleaved poly adenosine diphosphate ribose polymerase (PARP) by western blotting and caspase 3/8/9 multiple assay kit. We conclude that PITA can be used to efficiently cervical cancer studies, and promising findings have been obtained for further studies.

In vitro investigation of the effects of boron nitride nanotubes and curcumin on DNA damage.

BACKROUND: Stem cells provide an opportunity to analyse the effects of xenobiotic on cell viability, differentiation and cell functions. Evaluation of the possible cytotoxic and DNA damaging effects on bone marrow CD34+ stem cells is important for their ability to differentiate into blood cells, and also for bone marrow diseases therapy. Boron nitride nanotubes and curcumin are potential nanoformulation agents that can be used together in the treatment of cancer or bone marrow diseases. Therefore, it is important to evaluate their possible effects on different cell lines. OBJECTIVES: In this study, it was aimed to evaluate the cytotoxic and DNA damaging effects of boron nitride nanotubes which are commonly used in pyroelectric, piezoelectric and optical applications, but there is not enough information about its biocompatibility. Also, it was intended to research the effects of curcumin being used frequently in treatment processes for antioxidant properties. METHODS: The possible cytotoxic and DNA damaging effects of boron nitride nanotubes and curcumin on CD34+ cells, HeLa and V79 cells were evaluated by MTT assay and Comet assay, respectively. RESULTS AND CONCLUSION: Boron nitride nanotubes and curcumin had cytotoxic effects and cause DNA damage on CD34+ cells, HeLa and V79 cells at several concentrations, probably because of increased ROS level. However, there were not concentration - dependent effect and there were controversial toxicity results of the studied cell lines. Its mechanism needs to be enlightened by further analysis for potential targeted drug development. Graphical abstract.

Effects of developmental exposure to silver in ionic and nanoparticle form: A study in rats.

BACKGROUND: Evaluations of silver in both nanoparticle (Ag-NPs) and ionic forms indicate some adverse effects on living organisms, but little is known about their potential for developmental toxicity. In this study, developmental toxicity of Ag-NPs (from 0.2 to 20 mg/kg/day) and ionic Ag (AgNO3, 20 mg Ag/kg/day) were investigated in rats. METHODS: Animals were dosed by gavage from gestation day 7 - 20. The day after parturition, dams and pups were sacrificed and Ag level assessed in several maternal and pup organs. In addition, hepatotoxicity and oxidative stress parameters and histopathology were evaluated. RESULTS: No treatment related effects were found for gestational parameters including pregnancy length, maternal weight gain, implantations, birth weight and litter size at any dose level of Ag-NPs. Maternal weight gain was lower in dams receiving AgNO3 compared to the other groups, suggesting that the ionic form may exert a higher degree of toxicity compared to the NP form. Tissue contents of Ag were higher in all treated groups compared to control dams and pups, indicating transfer of Ag across the placenta. The findings furthermore suggest that Ag may induce oxidative stress in dams and their offspring, although significant induction was only observed after dosing with AgNO3. Histopathological examination of brain tissue revealed a high incidence of hippocampal sclerosis in dams treated with nanoparticle as well as ionic Ag. CONCLUSION: The difference in offspring deposition patterns between ionic and NP Ag and the observations in dam brain tissue, requires scrutiny, and, if corroborated, indicate that ionic and NP forms maybe need separate risk assessments and that the hazard ratings of silver in both ionic and nanoparticle forms should be increased, respectively. TRIAL REGISTRATION: Not applicable. Developmental Toxicity of Ag-NPs.