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Dietary intake of genistein suppresses hepatocellular carcinoma through AMPK-mediated apoptosis and anti-inflammation

Cited 14 time in Web of Science Cited 14 time in Scopus
Authors
Lee, Sang R; Kwon, Sun Woo; Lee, Young Ho; Kaya, Pelin; Kim, Jong Min; Ahn, Changhwan; Jung, Eui-Man; Lee, Geun-Shik; An, Beum-Soo; Jeung, Eui-Bae; Park, Bae-keun; Hong, Eui-Ju
Issue Date
2019-01-03
Publisher
BioMed Central
Citation
BMC Cancer, 19(1):6
Keywords
HCCGenisteinAMPKInflammationApoptosisPhytoestrogen
Abstract
Background
Women have a lower risk of hepatocellular carcinoma (HCC) than men, and the decreased possibility of HCC in women is thought to depend on estrogen levels. As a soybean-isoflavone product, genistein has estrogenic activity in various reproductive tissues, because it mimics 17β-estradiol and binds the estrogen receptor. Though genistein is a known liver cancer suppressor, its effects have not been studies in long-term experiment, where genistein is fed to a female animal model of HCC.

Methods
Mice were treated with diethylnitrosamine (DEN) to induce HCC at 2 weeks of age and fed with supplemental genistein for 5 months, from 40 to 62 weeks of age.

Results
The dietary intake of genistein decreased the incidence of HCC and suppressed HCC development. Genistein induced phospho-AMPK in total liver extracts, Hep3B cells, and Raw 264.7 cells, and phospho-AMPK promoted apoptosis in liver and Hep3B cells. Moreover, phospho-AMPK down-regulated pro-inflammatory responses and ameliorated liver damage. A suppressed pro-inflammatory response with increased mitochondrial respiration was concomitantly observed after genistein treatment.

Conclusions
Genistein-mediated AMPK activation increases hepatocyte apoptosis through energy-dependent caspase pathways, suppresses the inflammatory response in resident liver macrophages by increased cellular respiration, and consequently inhibits the initiation and progression of HCC.
ISSN
1756-6606
Language
English
URI
https://hdl.handle.net/10371/147079
DOI
https://doi.org/10.1186/s12885-018-5222-8
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College of Medicine/School of Medicine (의과대학/대학원)Xenotransplantation Research Center (바이오이종장기개발사업단)Journal Papers (저널논문_바이오이종장개개발사업단)
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