ROS-dependent Bax/Bcl2 and caspase 3 pathway-mediated apoptosis induced by zineb in human keratinocyte cells

Abstract

Daoud Ali,1 Abhilasha Tripathi,2 Hussain Al Ali,3 Yadvendra Shahi,2 Kamlesh K Mishra,2 Saud Alarifi,1 Abdullah A Alkahtane,1 Salem Manohardas1 1Department of Zoology, Science College, King Saud University, Riyadh, Saudi Arabia; 2CytoGene Research and Development, Lucknow, India; 3Centre of Excellence for Genomics, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia Abstract: There are a large number of agricultural workers who are exposed to pesticides through skin and inhalation. The best approach to identify altered molecular pathways during dermal exposure to pesticides is relevant to risk-associated concern about skin safety. In this study, we investigated the cytotoxic effect of zineb, a fungicide, in human keratinocyte (HaCaT) cells. HaCaT cells were treated with zineb (1–40 µg/mL) for 24 hours. Cellular and molecular mechanisms of cell toxicity were investigated through MTT and neutral red-uptake assays. Zineb reduced viability of HaCaT cells and induced apoptosis in a concentration-dependent manner. Zineb increased levels of Bax and caspase 3 and inhibited the level of Bcl2, which subsequently induced apoptosis via the Bax/Bcl2 and caspase pathway. Therefore, zineb could have induced apoptosis through the mitochondrial pathway in HaCaT cells. Our study suggests that zineb is cytotoxic to HaCaT cells via the induction of apoptosis and oxidative stress in vitro. Keywords: zineb, HaCaT cells, apoptosis, MTT assay, DNA damage

Keywords

• Zineb
• HaCaT cells
• Apoptosis
• Cytotoxic effect