Abstract 1899: Induction of phase 2 antioxidant genes by the aqueous extract of Matricaria chamomilla (Chamomile) through Keap1-Nrf2 signaling pathway

Abstract

Abstract Induction of phase 2 detoxifying enzymes in response to naturally occurring agents provides an effective means of protection against oxidative stress. Increasing lines of evidence show that the Keap1-Nrf2 complex is a key molecular target of phase 2 enzyme inducers. The transcription factor Nrf2 is a member of basic leucine-zipper NF-E2 family and interacts with the antioxidant response element (ARE) in the promoter region of phase 2 detoxifying enzymes. A cytoplasmic actin-binding protein, Keap1, is an inhibitor of Nrf2 and sequesters it in the cytoplasm. Various extracellular stimuli and inducers dissociate this complex, allowing Nrf2 to translocate into the nucleus, binding with ARE and induce the expression of various antioxidant genes. Recently natural compounds have been established as activators of phase 2 antioxidant enzymes through Nrf2 signaling pathway. We used aqueous chamomile extract obtained from dried flowers to investigate its effect on Nrf2 activation and induction of phase 2 enzymes in human prostate cancer PC-3 and LNCaP cells. Treatment of these cells with chamomile at 1-40μM concentration equivalent to aglycone apigenin caused significant dissociation of Keap1 from the Keap1-Nrf2 complex with significant decrease of Keap1 in the cytoplasm in dose- and time- dependent fashion. Similarly, a marked decrease in Nrf2 was observed in the cytoplasm after chamomile treatment. Chamomile treatment further led to increase in phase 2 enzymes including superoxide dismutase, NAD(P)H dehydrogenase [quinone] 1 and catalase in these cells which correlated with nuclear Nrf2 expression in dose- and time- dependent manner. Taken together, these molecular evidences provide an insight into the mechanism underlying the induction of phase 2 enzymes through Keap1- Nrf2 signaling pathway by chamomile, endorsing its antioxidant function. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1899.