Inhibition of cell growth and induction of inflammation by endosulfan in HUVEC-C cells.

Endosulfan is one of the organochlorine pesticides. It has been associated with a wide range of adverse health effects. However, it is unknown whether endosulfan causes endothelial dysfunction. In the present study, we investigated the effects of endosulfan on human vascular endothelial cells. We exposed human umbilical vein endothelial cells (HUVEC-C) to varying concentrations of endosulfan for 48 h. The results showed that endosulfan lowered cell viability and inhibited cell proliferation in a dose-dependent manner. Flow cytometric analysis showed that endosulfan at 60 μM induced G1 cell cycle arrest, a response attributed to down-regulation of CDK6 and pRb dephosphorylation. We observed that endosulfan at 40 and 60 μM induced a considerable percentage of cells to undergo apoptosis, as detected by Annexin-V binding assays. Endosulfan reduced mitochondrial transmembrane potential, leading to the release of cytochrome c into the cytoplasm; meanwhile, endosulfan also inhibited the mRNA expression level of survivin, which resulted in the activation of caspase-3. These results indicated that the intrinsic mitochondria-mediated pathway was involved in apoptotic process. Exposure to endosulfan increased the secretion and mRNA expression levels of inflammation factors interleukin (IL)-6 and IL-8, suggesting that endosulfan could cause inflammation. Overall, these findings suggested that endosulfan is toxic to HUVEC-C cells, resulting in endothelial dysfunction.