Abrogation of Akt signaling by Isobavachalcone contributes to its anti-proliferative effects towards human cancer cells.

Abstract:

:Akt signaling pathway has attracted much attention as a promising target for cancer therapeutics. Herein, we report that Isobavachalcone (IBC), a natural chalcone, potently abrogates Akt signaling and exerts anti-proliferative effects on several human cancer cell lines. Modeling results from the Sybyl/FlexiDock program suggest that IBC potentially binds to the ATP-binding pocket of Akt, which is confirmed by the observations that IBC inhibits Akt1 kinase in vitro. Further studies reveal that IBC significantly abates Akt phosphorylation at Ser-473 and Akt kinase activity in cells, which subsequently leads to inhibition of Akt downstream substrates and evokes significant levels of apoptosis associated with mitochondria pathway.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Jing H,Zhou X,Dong X,Cao J,Zhu H,Lou J,Hu Y,He Q,Yang B

doi

10.1016/j.canlet.2010.01.035

subject

Has Abstract

pub_date

2010-08-28 00:00:00

pages

167-77

issue

2

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(10)00070-4

journal_volume

294

pub_type

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