Molecular basis of arsenite (As⁺³)-induced acute cytotoxicity in human cervical epithelial carcinoma cells

Abstract

BackgroundRapid industrialization is discharging toxic heavy metals into the environment, disturbing human health in many ways and causing various neurologic, cardiovascular, and dermatologic abnormalities and certain types of cancer. The presence of arsenic in drinking water from different urban and rural areas of the major cities of Pakistan, for example, Lahore, Faisalabad, and Kasur, was found to be beyond the permissible limit of 10 parts per billion set by the World Health Organization. Therefore the present study was initiated to examine the effects of arsenite (As+3) on DNA biosynthesis and cell death.MethodsAfter performing cytotoxic assays on a human epithelial carcinoma cell line, expression analysis was done by quantitative polymerase chain reaction, western blotting, and flow cytometry.ResultsWe show that As+3 ions have a dose- and time-dependent cytotoxic effect through the activation of the caspase-dependent apoptotic pathway. In contrast to previous research, the present study was designed to explore the early cytotoxic effects produced in human cells during exposure to heavy dosage of As+3 (7.5 µg/ml). Even treatment for 1 h significantly increased the mRNA levels of p21 and p27 and caspases 3, 7, and 9. It was interesting that there was no change in the expression levels of p53, which plays an important role in G2/M phase cell cycle arrest.ConclusionOur results indicate that sudden exposure of cells to arsenite (As+3) resulted in cytotoxicity and mitochondrial-mediated apoptosis resulting from up-regulation of caspases.

In vitro antibiofilm and anti‐adhesion effects of magnesium oxide nanoparticles against antibiotic resistant bacteria

“…The observed cellular deformities included extensive vacuolation, contact loss, cell rounding and lysis. These cellular alterations may have been attributable to reactiveness of metal cations and generation of ROS . These researchers’ findings indicate that at higher concentrations NPs react with biomolecules and produce ROS, leading to the cell death.…”

Induction of telomere shortening and cellular apoptosis by sodium meta-arsenite in human cancer cell lines

“…The BAX, caspase 3 and caspase 9 protein are generally related with the intrinsic apoptotic pathway (Dewson and Kluck 2009 ). In several other studies, it has also been reported that altering Bcl-2 family proteins and activating the intrinsic pathway are induced for apoptosis in human mesenchymal stem cells (Yadav et al 2010 ) and cytotoxic effect through the activation of the intrinsic caspase-dependent apoptotic pathway is displayed in the human epithelial carcinoma cell line treated with arsenite (Arshad et al 2015 ). Besides, we have demonstrated that the increased stress-related proteins, such as p21, HSP 70 and HSP 90, are also observed by SMA treatment.…”

“…Besides, we have demonstrated that the increased stress-related proteins, such as p21, HSP 70 and HSP 90, are also observed by SMA treatment. The expression level of p21 was increased by arsenite treatment in the human epithelial carcinoma cells (Arshad et al 2015 ). And the increased p21 protein also induced the intrinsic apoptosis pathway and arrest of cell cycle (Cao et al 2003 ).…”