Activation of AMP‐activated protein kinase on human gastric cancer cells by apoptosis induced by corosolic acid isolated from Weigela subsessilis

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 μm. Corosolic acid also triggered the activation of caspase‐3 and poly (ADP‐ribose) 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 © 2010 John Wiley & Sons, Ltd.

[1]  N. Sonenberg,et al.  mTOR signaling: implications for cancer and anticancer therapy , 2005, British Journal of Cancer.

[2]  K. Inoki,et al.  TSC2 Mediates Cellular Energy Response to Control Cell Growth and Survival , 2003, Cell.

[3]  J. Gutterman,et al.  A plant triterpenoid, avicin D, induces autophagy by activation of AMP-activated protein kinase , 2007, Cell Death and Differentiation.

[4]  G. Mills,et al.  Synergistic augmentation of rapamycin-induced autophagy in malignant glioma cells by phosphatidylinositol 3-kinase/protein kinase B inhibitors. , 2005, Cancer research.

[5]  H. Ngan,et al.  Inhibition of Cervical Cancer Cell Growth through Activation of Upstream Kinases of AMP-Activated Protein Kinase , 2009, Tumor Biology.

[6]  D. Hardie.  The AMP-activated protein kinase pathway – new players upstream and downstream , 2004, Journal of Cell Science.

[7]  K. Bae,et al.  Anti-complementary activity of ursane-type triterpenoids from Weigela subsessilis. , 2006, Biological & pharmaceutical bulletin.

[8]  P. Houghton,et al.  mTOR and cancer therapy , 2006, Oncogene.

[9]  K. Ahn,et al.  Corosolic acid isolated from the fruit of Crataegus pinnatifida var. psilosa is a protein kinase C inhibitor as well as a cytotoxic agent. , 1998, Planta medica.

[10]  J. R. Kelley,et al.  Gastric cancer epidemiology and risk factors. , 2003, Journal of clinical epidemiology.

[11]  Shailendra Giri,et al.  5-Aminoimidazole-4-carboxamide-1-β-D-ribofuranoside Inhibits Cancer Cell Proliferation in Vitro and in Vivo via AMP-activated Protein Kinase* , 2005, Journal of Biological Chemistry.

[12]  R. Berlinck,et al.  Marine organisms as a source of new anticancer agents. , 2001, The Lancet. Oncology.

[13]  J. Haerting,et al.  Chemotherapy in advanced gastric cancer: a systematic review and meta-analysis based on aggregate data. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[14]  Yuquan Wei,et al.  Triterpene acids isolated from Lagerstroemia speciosa leaves as α‐glucosidase inhibitors , 2009, Phytotherapy research : PTR.

[15]  R. Memmott,et al.  Akt-dependent and -independent mechanisms of mTOR regulation in cancer. , 2009, Cellular signalling.

[16]  K. Bae,et al.  Inhibitory effect of coumarins from Weigela subsessilis on low density lipoprotein oxidation. , 2005, Biological & pharmaceutical bulletin.

[17]  K. Guan,et al.  AMP‐activated protein kinase and cancer , 2009, Acta physiologica.

[18]  Jeong Eon Lee,et al.  Berberine Inhibits Growth of the Breast Cancer Cell Lines MCF-7 and MDA-MB-231 , 2008, Planta medica.

[19]  A. Jimeno,et al.  HER2 in gastric cancer: a new prognostic factor and a novel therapeutic target. , 2008, Annals of oncology : official journal of the European Society for Medical Oncology.

[20]  Ruiliang Ge,et al.  Corosolic acid induces apoptosis through mitochondrial pathway and caspase activation in human cervix adenocarcinoma HeLa cells. , 2009, Cancer letters.