New insight into the enantioselective cytotoxicity of cypermethrin: imbalance between cell cycle and apoptosis

Cypermethrin (CP) is a frequently used chiral pesticide comprised of different enantiomers that can induce a variable toxic response in biota, dependent on conformational change. However, the potential mechanism accounting for the enantioselective toxicity induced by CP enantiomers remains unknown. Herein, to shed light on the underlying mechanism of enantioselective cytotoxicity on cell cycle and apoptotic function, an MTT assay, flow cytometric (FCM) approach, and qPCR arrays combining bioinformatic analysis were conducted on HepG2 cell lines following exposure to CP enantiomers. Decreased cell viability in keeping with increased cell arrest and apoptosis was observed in cells exposed to (1S,3R,αR)-CP, relative to the (1R,3S,αS)-CP treatment group. PCR array also reflected an enantioselective difference in expression of cell cycle and apoptosis-related genes. Ingenuity pathway analysis (IPA) showed that cell cycle checkpoints, arrest in interphase, death receptor signaling, and apoptosis were among the top canonical and disease and functions predicted to be affected between CP enantiomers. Data presented here not only provide potential molecular endpoints for evaluating toxicity by cell cycle and apoptosis but also help to guide the scientific application of chiral pesticides.