Induction of the Phase II Detoxification Enzyme NQO1 in Hepatocarcinoma Cells by Lignans from the Fruit of Schisandra chinensis through Nuclear Accumulation of Nrf2

Title
Induction of the Phase II Detoxification Enzyme NQO1 in Hepatocarcinoma Cells by Lignans from the Fruit of Schisandra chinensis through Nuclear Accumulation of Nrf2
Authors
이샛별김철영이희주윤지호노주원
Keywords
Quinone reductase; Detoxification; Lignans; Schisandra chinensis Baillon; Nrf2; Magnoliaceae; tigloylgomisin H
Issue Date
2009-10
Publisher
Planta medica
Citation
VOL 75, NO 12, 1314-1318
Abstract
The upregulation of phase II detoxification genes is believed to play an important role in cancer prevention. The molecular mechanism underlying the changes in gene expression that accompany cancer prevention involves activation of the transcription factor, NF-E2-related factor 2 (Nrf2). In traditional medicine, the fruit of SCHISANDRA CHINENSIS Baill is used as a tonic, an anti-tussive and an anti-aging drug. In the current study, nine lignans were isolated from S. CHINENSIS and tested for their ability to induce quinone reductase (QR) activity in Hepa1c1c7 mouse hepatocarcinoma cells. Tigloylgomisin H (TGH) and angeloylgomisin H (AGH) significantly induced QR activity and exhibited a relatively high chemoprevention index (CI) (10.80 and 4.59, respectively) as compared to control. TGH also induced QR activity in BPrc1 mouse hepatocarcinoma cells as well, which are defective in aryl hydrocarbon nuclear translocator (Arnt). In HepG2 human hepatocarcinoma cells, TGH significantly activated gene expression mediated by the antioxidant response element (ARE), a key regulatory region in the promoters of detoxification enzymes, through the nuclear accumulation of Nrf2. The results of the current study suggest that TGH functions as a novel monofunctional inducer that specifically upregulates phase II enzymes through the Nrf2-ARE pathway. TGH thus represents a potential liver cancer prevention agent.
URI
http://pubs.kist.re.kr/handle/201004/35318
ISSN
0032-0943
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KIST Publication > Article
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