Abstract
Cellular damage by reactive oxygen species (ROS) causes aging and remains major factor in the development of various human diseases including diabetes, liver diseases, neurodegenerative and cardiovascular diseases, including cancer. Dietary antioxidants have been considered as an attractive strategy to prevent or attenuate the progression of diseases caused by oxidative stress. Induction of phase 2 detoxifying enzymes in response to naturally occurring agents provides an effective means of protection against oxidative stress. Aqueous extract of chamomile (Matricaria chamomilla) in the form of tea has been used for centuries to treat various inflammatory conditions supporting its traditional use for treating various human ailments. We used aqueous chamomile extract obtained from dried flowers to investigate its effect on Nrf2 activation and induction of phase 2 enzymes in RAW 264.7 murine macrophages and H2O2 as an agent for oxidative stress. Treatment with 50 µM H2O2 for 6 h caused significant increase in cellular stress accompanied by cell death in RAW 264.7 murine macrophages as evident from light microscopy and annexin-V FITC assay. Pre-treatment with chamomile at 10, 20 and 40 µg for 16 h followed by H2O2 treatment protected cell death caused by excessive ROS generation and prevented H2O2-mediated inhibition of cell growth. Chamomile exposure significantly increased the expression of antioxidant enzymes viz. peroxiredoxin (Prx), thioredoxin (Trx) and heme oxygenase (HO-1) in a dose-dependent manner, compared with their respective controls. Furthermore, chamomile exposure to RAW 264.7 murine macrophages increased the nuclear translocation of Nrf2 with increased phosphorylated Nrf2 levels, and it's binding to the antioxidant response element (ARE) in the nucleus. These data provide evidence that chamomile induces the expression of cytoprotective antioxidant enzyme (HO-1) and other redox regulatory enzymes (Prx and Trx) in response to the nuclear translocation of a key redox sensitive transcription factor Nrf2 from the cytoplasm and provide protection from cytotoxicity caused by inflammatory oxidants. Understanding chamomile-mediated molecular events could play a potentially important role in setting up strategies for prevention and treatment of various human diseases including cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4626. doi:10.1158/1538-7445.AM2011-4626