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Anthocyanins target AMPK/mTOR and AMPK/Wnt pathways in exerting anti‐tumor effects in colon cancer or hepatocarcinoma cells
Author(s) -
YunKyoung Lee,
Park Song Yi,
Kim YoungMin,
Lee Won Sup,
Park Ock Jin
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.lb259
Subject(s) - ampk , pi3k/akt/mtor pathway , wnt signaling pathway , chemistry , cell growth , microbiology and biotechnology , cancer research , mechanistic target of rapamycin , signal transduction , protein kinase a , phosphorylation , biology , biochemistry
AMP‐activated kinase, a sensor of cellular energy status, has emerged as a potent target for cancer prevention and/or treatment. Thus, the application of dietary origin AMPK activators could link to an effective strategy of cancer control. We have found that the activation of AMPK with anthocyanin extracted from Meoru exerted growth inhibitory effects through regulation of mTOR or GSK3β/β‐catenin pathway in HT‐29 colon and Hep3B cells respectively. In both types of cancer cells, the growth signal IGF‐1 stimulated mTOR or Wnt pathway components. AMPK appeared to inhibit phosphorylation of mTOR possibly through interacting with one of the subunit, raptor. The effect of anthocyanins on cancer cell survival and AMPK/mTOR pathway was compared with a classical mTOR inhibitor rapamycin, and anthocyanins were found to inhibit growth through mTOR comparable to rapamycin. Moreover, anthocyanins stimulated β‐catenin degradation through GSK3β activation, and it seemed to be regulated by AMPK. This work has shown that the cell energy controller AMPK can control two important cell growth regulators mTOR and Wnt, and the modulation of AMPK/mTOR or AMPK/Wnt pathways by phytochemicals such as anthocyanins can further strengthen the use of phytochemicals for cancer control. [This work was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MEST) (NO. R01‐2008‐000‐20131‐0)]