Activation of AMP-activated Protein Kinase on Human Gastric Cancer Cells by Apoptosis Induced by Corosolic Acid Isolated from Weigela subsessilis

被引:28
作者
Lee, Myung Sun [3 ]
Lee, Chang Min [6 ]
Cha, Eun Young [3 ]
Thuong, Phuong Thien [4 ]
Bae, KiHwan [5 ]
Song, In Sang [1 ,2 ,6 ]
Noh, Seung Moo [1 ,2 ,6 ]
Sul, Ji Young [1 ,2 ,6 ]
机构
[1] Chungnam Natl Univ, Sch Med, Dept Surg, Taejon 301747, South Korea
[2] Chungnam Natl Univ, Sch Med, Res Inst Med Sci, Taejon 301747, South Korea
[3] Chungnam Natl Univ Hosp, Reg Canc Inst, Taejon, South Korea
[4] Vietnam Natl Inst Med Mat, Hanoi, Vietnam
[5] Chungnam Natl Univ, Coll Pharm, Taejon, South Korea
[6] Chungnam Natl Univ Hosp, Dept Surg, Taejon, South Korea
关键词
corosolic acid; gastric cancer; AMPK; apoptosis; MTOR; AUTOPHAGY; UPSTREAM; PATHWAY; GROWTH;
D O I
10.1002/ptr.3210
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Corosolic acid is one of the triterpenoids present in the leaves of Weigela subsessilis. The antidiabetic activity of corosolic acid has been reported previously, but to date, the anticancer effects on gastric cancer have been poorly studied. In this study, corosolic acid showed growth inhibition on SNU-601 human gastric cancer cells, with an IC50 value of 16.9 +/- 2.9 mu M. Corosolic acid also triggered the activation of caspase-3 and poly (ADPribose) polymerase, while it was recovered by Z-VAD-FMK. Moreover, the cell growth/apoptosis activities of corosolic acid were regulated by the AMP-activated protein kinase-mammalian target of rapamycin (AMPK-mTOR) signals. These results showed that corosolic acid-mediated AMPK activation leads to inhibition of mTOR, thus providing a possible mechanism of action of corosolic acid in the inhibition of cancer cell growth and the induction of apoptosis. Copyright (C) 2010 John Wiley & Sons, Ltd.
引用
收藏
页码:1857 / 1861
页数:5
相关论文
共 20 条
[1]   Corosolic acid isolated from the fruit of Crataegus pinnatifida var. psilosa is a protein kinase C inhibitor as well as a cytotoxic agent [J].
Ahn, KS ;
Hahm, MS ;
Park, EJ ;
Lee, HK ;
Kim, IH .
PLANTA MEDICA, 1998, 64 (05) :468-470
[2]   mTOR and cancer therapy [J].
Easton, J. B. ;
Houghton, P. J. .
ONCOGENE, 2006, 25 (48) :6436-6446
[3]   HER2 in gastric cancer: a new prognostic factor and a novel therapeutic target [J].
Gravalos, C. ;
Jimeno, A. .
ANNALS OF ONCOLOGY, 2008, 19 (09) :1523-1529
[4]   The AMP-activated protein kinase pathway - new players upstream and downstream [J].
Hardie, DG .
JOURNAL OF CELL SCIENCE, 2004, 117 (23) :5479-5487
[5]   Triterpene Acids Isolated from Lagerstroemia speciosa Leaves as α-Glucosidase Inhibitors [J].
Hou, Wenli ;
Li, Yanfang ;
Zhang, Qiang ;
Wei, Xin ;
Peng, Aihua ;
Chen, Lijuan ;
Wei, Yuquan .
PHYTOTHERAPY RESEARCH, 2009, 23 (05) :614-618
[6]   TSC2 mediates cellular energy response to control cell growth and survival [J].
Inoki, K ;
Zhu, TQ ;
Guan, KL .
CELL, 2003, 115 (05) :577-590
[7]   Gastric cancer epidemiology and risk factors [J].
Kelley, JR ;
Duggan, JM .
JOURNAL OF CLINICAL EPIDEMIOLOGY, 2003, 56 (01) :1-9
[8]   Berberine inhibits growth of the breast cancer cell lines MCF-7 and MDA-MB-231 [J].
Kim, Jong Bin ;
Lee, Kyung-Min ;
Ko, Eunyoung ;
Han, Wonshik ;
Lee, Jeong Eon ;
Shin, Incheol ;
Bae, Ji-Yeon ;
Kim, Sangmin ;
Noh, Dong-Young .
PLANTA MEDICA, 2008, 74 (01) :39-42
[9]   Akt-dependent and -independent mechanisms of mTOR regulation in cancer [J].
Memmott, Regan M. ;
Dennis, Phillip A. .
CELLULAR SIGNALLING, 2009, 21 (05) :656-664
[10]   mTOR signaling: implications for cancer and anticancer therapy [J].
Petroulakis, E ;
Mamane, Y ;
Le Bacquer, O ;
Shahbazian, D ;
Sonenberg, N .
BRITISH JOURNAL OF CANCER, 2006, 94 (02) :195-199