求助一篇文献 谢谢

songxinxing

4 `. Q9 w6 P8 a- n5 \; S8 n+ Y- ?  t6 p" ?0 F
http://www.spandidos-publications.com/ijo/40/2/5012 o* [5 R$ |+ i$ @' c
) ^7 @* j4 j8 D' V9 {/ o9 M' e
Activation of AMP-kinase by AICAR induces apoptosis of DU-145 prostate cancer cells through generation of reactive oxygen species and activation of c-Jun N-terminal kinase
: Q; K! ?+ x; E: x3 C* Z3 t$ ?- K' H5 g* f
Authors: Heinrich Sauer, Steffi Engel, Nada Milosevic, Fatemeh Sharifpanah, Maria Wartenberg ( n7 `4 i1 E3 w: `- Q& J' [1 R7 m6 T

" `6 z5 e" {8 c7 u9 j/ i9 Q* j! nAffiliations: Department of Physiology, Justus Liebig University Giessen, Aulweg 129, D-35392 Giessen, Germany
5 V" n; p% ~9 h. L
7 d3 u) L: {9 H" {  J, ]9 X- mPublished online on: Thursday, October 13, 2011 : B, k& ~4 s- ?; g4 ?+ p0 _

( W  m6 {7 A% H* Z6 t4 Z8 t+ xDoi: 10.3892/ijo.2011.1230 ! N- D6 b2 C$ c- {) N9 x

" z3 u& Q1 l. Z. NPages: 501-508 1 y0 _2 G, N2 P( e& ^1 f
+ v) F- w5 |- n- X( m! ^
Abstract:
6 w) C2 r3 Z: }( S5 @, {The growth of cancer cells is limited by energy supply which is regulated by the energy sensor AMP-kinase (AMPK). Hence, mimicking a low energy state may inhibit cancer growth and may be exploited in anticancer therapies. In the present study, the impact of AMPK activation on cell growth and apoptosis of DU-145 prostate cancer cells was investigated. Incubation with the AMPK activator aminoimidazole carboxamide ribonucleotide (AICAR) dose-dependently inhibited cell growth, activated AMPK, and inhibited mTOR. Furthermore, AICAR treatment activated c-Jun N-terminal kinase (JNK) and caspase-3, thereby initiating apoptosis. Within 60 min of treatment AICAR raised intracellular reactive oxygen species (ROS) which could be abolished in the presence of the free radical scavenger N-(2-mercaptopropionyl)glycin (NMPG), the AMPK inhibitor compound C (Comp C) and the respiratory chain complex I inhibitor rotenone, but not by the NADPH oxidase inhibitor VAS2870. Inhibition of ROS generation abolished AMPK activation by AICAR as well as JNK and caspase-3 activation. Furthermore, AMPK activation, JNK phosphorylation and cleaved caspase-3 upon AICAR treatment were abolished in the presence of Comp C. In summary, our data demonstrate that activation of AMPK by AICAR induces apoptosis of prostate
% f) x" F! {; P! e' m! d : y( ~4 H% }% p+ G& K3 ^: a

ivantanqi

FYI