title: Pro-apoptotic and migration-suppressing potential of EGCG, and the involvement of AMPK in the p53-mediated modulation of VEGF and MMP-9 expression.
abstract: The present study investigated the regulatory mechanisms by which epigallocatechin-3-gallate (EGCG) exerts vascular endothelial growth factor (VEGF)-, p53- and AMP-activated protein kinase (AMPK)-associated pro-apoptotic and migration-suppressing effects on colon cancer cells. EGCG decreased the expression levels of VEGF and matrix metalloproteinase (MMP)-9. EGCG treatment induced apoptosis in the presence of wild-type and mutant p53, indicating that a p53-independent pathway may contribute to EGCG-induced apoptosis in these cells. EGCG showed migration-suppressing effects, suggesting that this activity may also have p53-dependent and -independent components. The interaction between p53 and VEGF in the EGCG-treated cells was investigated using pifithrin-α. Notably, the suppression of p53 activity blocked the ability of EGCG to inhibit VEGF and MMP-9 in the cells expressing wild-type p53, but not mutant p53, indicating that the effects of EGCG on VEGF may be p53-dependent or -independent. Finally, although AMPK and VEGF did not appear to co-localize, the results indicated that AMPK controls VEGF in EGCG-treated cells regardless of the p53 status.
authors.affiliation: Department of Biological Sciences and Biotechnology, Hannam University Daedeok Valley Campus, Yuseong-gu, Daejeon 305-811, Republic of Korea.
authors.forename: Song Yi
authors.initials: SY
authors.lastname: Park
authors.forename: Chang Hee
authors.initials: CH
authors.lastname: Jung
authors.forename: Bokyung
authors.initials: B
authors.lastname: Song
authors.forename: Ock Jin
authors.initials: OJ
authors.lastname: Park
authors.forename: Young-Min
authors.initials: YM
authors.lastname: Kim
keywords: epigallocatechin-3-gallate; matrix metalloproteinase-9; migration-suppressing effects; p53; vascular endothelial growth factor