α-Pinene Triggers Oxidative Stress and Related Signaling Pathways in A549 and HepG2 Cells

The volatile organic compounds (VOCs) -d-limonene, alpha-pinene, and isoprene- are widely used in scented products including food flavorings, air fresheners, and cosmetics. The effects of these VOCs on cell viability, oxidative stress generation, and the related molecular events were investigated in A549 and HepG2 cells. alpha-Pinene induced cell death, reactive oxygen species (ROS) generation, and reporter gene activities of antioxidant response element (ARE), activator protein 1 (AP-1), and nuclear factor (NF)-kappa B. alpha-Pinene stimulated the redox-sensitive transcription factors such as nuclear factor E2-related factor 2 (Nrf2) and NF-kappa B. Their down stream targets including heme oxygenase 1, inducible nitric oxide synthase, and cyclooxygenase 2 also increased after treatment with alpha-pinene. Moreover, alpha-pinene-induced oxidative stress-related signaling pathways could be connected by mitogen-activated protein kinases. Conversely, alpha-pinene-mediated cell death, ROS formation, and AP-1 induction were inhibited by an antioxidant, N-acetyl-L-cysteine. Thus, alpha-pinene can induce the cell death possibly by modulating oxidative stress-related signaling pathways which can be reversed by an antioxidant treatment.