Involvement of AMPK in the regulation of CSK, COX‐2 and mTOR in cancer cell growth control under EGCG treatment

Abstract

Epigallocatechin gallate (EGCG) was recently shown to activate the AMP‐activated protein kinase (AMPK) in cancer cells and in vivo systems. In the lieu of elucidating the mechanism for this effect and the consequence of the activation of AMPK on the important signals of cancer cell control‐CSK, COX‐2 and mTOR, we have applied Hep3B and HT‐29 cancerous cells. We have shown that EGCG activated AMPK possibly through stimulation of AMPK. The activation of AMPK with EGCG suppressed the expression of CSK as well as COX‐2 and mTOR. EGCG induced the translocation of AMPK into nucleus. Upon the inactivation of AMPK either by AMPK siRNA or Compound C, EGCG no longer modulated CSK or COX‐2 or mTOR implying that AMPK is an upstream signal for these molecules. With fluorescent markers of AMPK, CSK and COX‐2 with or without the activation of AMPK, it was shown that EGCG stimulated the translocation of AMPK and CSK into the nucleus. However, without the activation of AMPK via Compound C, the stimulatory effect of EGCG on the translocation into the nucleus was diminished. Therefore, the activation of AMPK and the translocation of AMPK into the nucleus seem to be necessary for EGCG to control cancer cell growth and further the regulation of CSK, COX‐2 and mTOR. [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)]Grant Funding Source: Korea Science and Engineering Foundation