The anti-tumourigenic effect of ellagic acid in SKOV-3 ovarian cancer cells entails activation of autophagy mediated by inhibiting Akt and activating AMPK.
Clin Exp Pharmacol Physiol. 2020 Sep ;47(9):1611-1621. Epub 2020 Jun 23. PMID: 32415699
Fahmy G Elsaid
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 ICof 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) and 4EBP-1 (Thr), two downstream targets of mTORC1, and p-Akt (Thr) but increased levels of AMPK (Thr) and p-raptor (Ser), 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.