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.
Lee
Myung Sun
MS
Regional Cancer Institute, Chungnam National University Hospital, Daejeon, Korea.
Lee
Chang Min
CM
Cha
Eun Young
EY
Thuong
Phuong Thien
PT
Bae
KiHwan
K
Song
In Sang
IS
Noh
Seung Moo
SM
Sul
Ji Young
JY
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D027922:Caprifoliaceae / Q000737:chemistry*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D018515:Plant Leaves / Q000737:chemistry; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D014315:Triterpenes; C113861:corosolic acid; D011065:Poly(ADP-ribose) Polymerases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; C505407:CASP3 protein, human; D053148:Caspase 3