Propoxur

Propoxur is a reversible, competitive, orally active AChE inhibitor that can cross the blood-brain barrier. Propoxur inhibits AChE activity to induce neurotoxicity, while promoting MMP-2 expression and enhancing tumor cell migration and invasion by inducing intracellular ROS generation and activating the ERK/Nrf2 signaling pathway. On the one hand, Propoxur inhibits AChE, leading to acetylcholine accumulation and causing neurological dysfunction; on the other hand, it promotes Nrf2 nuclear translocation through ROS-dependent ERK1/2 phosphorylation, and upregulates MMP-2 and other invasion-related proteins. Propoxur is also a carbamate insecticide used to combat turf, forestry, and household pests^[1][2][3]. In Vitro:Propoxur (0.01-100 μM; 48 h) promotes cell migration and invasion in human breast cancer MCF-7 and MDA-MB-231 cells in a concentration-dependent manner, enhances MMP-2 protein expression, increases intracellular ROS levels, and activates ERK1/2 phosphorylation and Nrf2 nuclear translocation^[1]. The intracellular regulatory activity of Propoxur could be reversed by PD98059 (HY-12028)^[1].
Propoxur (10 μg/mL; 24 h) induces lipid peroxidation in hamster ovary CHO-K1 cells, significantly increases MDA production, decreases GSH content and GSH/GSSG ratio, and activates GR, GPx, and GST antioxidant enzyme activities. BSO pretreatment further aggravated oxidative damage^[2]. In Vivo:Propoxur (8.51 mg/kg/day; oral; 30 days) induces oxidative stress in brain regions (cerebellum, cortex, hippocampus) in rats, manifestes by lipid peroxidation (increased MDA), protein carbonylation (increased PCC), decreases GSH levels and decreased activities of antioxidant enzymes (SOD, CAT, GSH-Px, GST), while inhibiting acetylcholinesterase (AChE) activity. Pretreatment with essential oil extracted from Nigella sativa significantly improves the above indicators^[3].