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Regulation of AMPK‐beta‐catenin pathway via GSK3beta dependently or independently in Hep3B cancer cell growth and apoptosis control with selenium
Author(s) -
Park Song Yi,
Lee YunKyoung,
Kim YoungMin,
Park Ock Jin
Publication year - 2013
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.27.1_supplement.639.1
Subject(s) - ampk , chemistry , microbiology and biotechnology , signal transduction , apoptosis , catenin , chromosomal translocation , protein kinase a , phosphorylation , cancer research , cancer cell , cancer , medicine , wnt signaling pathway , biology , biochemistry , gene
This study approached to address the mechanism of cancer cell suppressive activities of selenium and the consequence of the activation of AMPK on the important signal of cancer cell survival β‐catenin. We have shown that selenium activated AMPK, and the activation of AMPK with selenium suppressed β‐catenin. Selenium induced the translocation of AMPK into nucleus, and prevented the accumulation of β‐catenin, a prime regulatory molecule of many oncogenic genes into nucleus. Upon the inactivation of AMPK either by AMPK siRNA or Compound C, selenium no longer modulated β‐catenin implying that AMPK is an upstream signal for β‐catenin. By applying fluorescent markers of nucleus, AMPK and β‐catenin, it was shown that selenium down‐regulated expressions of β‐catenin and AMPK and β‐catenin were clustered together right outside of nuclear membrane. In the AMPK inactivated states with AMPK siRNA the translocation into nucleus of both these signals was facilitated under selenium treatment. Also, we have found that cancer cell anti‐proliferative effect of selenium was mediated by a GSK3β dependent AMPK/GSK3β/β‐catenin or GSK3β independent AMPK/β‐catenin pathway. These findings imply that selenium has a chemopreventive potential through the regulation of AMPK involving a complex downstream signaling pathways of β‐catenin. [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)]