The anti‐tumourigenic effect of ellagic acid in SKOV‐3 ovarian cancer cells entails activation of autophagy mediated by inhibiting Akt and activating AMPK
Abstract
This study investigated the effect of ellagic acid (EA) on SKOV‐3 cell growth and invasiveness and tested if the underlying mechanism involves modulating autophagy. Cells were treated with EA in the presence or absence of chloroquine (CQ), an autophagy inhibitor, compound C (CC), an AMPK inhibitor, or an insulin‐like growth factor‐1 (IGF‐1), a PI3K/Akt activator. EA, at an IC
50
of 36.6 µmol/L, inhibited cell proliferation, migration, and invasion and induced cell apoptosis in SKOV‐3 cells. These events were prevented by CQ. Also, EA increased levels of Beclin‐1, ATG‐5, LC3I/II, Bax, cleaved caspase‐3/8 and reduced those of p62 and Bcl‐2 in these cancer cells. Mechanistically, EA decreased levels of p‐S6K1 (Thr
389
) and 4EBP‐1 (Thr
37/46
), two downstream targets of mTORC1, and p‐Akt (Thr
308
) but increased levels of AMPK (Thr
172
) and p‐raptor (Ser
792
), a natural inhibitor of mTORC1. CC or IGF‐1 alone partially prevented the effect of EA on cell survival, cell invasions, and levels of LDH, Beclin‐1, and cleaved caspase‐3. In conclusion, EA can inhibit SKOV‐3 growth, migration, and invasion by activating cytotoxic autophagy mediated by inhibition of mTORC1 and Akt and activation of AMPK.
