Exendin-4 induces cytotoxic autophagy in two ovarian cancer cell lines through inhibition of Mtorc1 mediated by activation of AMPK and suppression of akt

Title:

Exendin-4 induces cytotoxic autophagy in two ovarian cancer cell lines through inhibition of Mtorc1 mediated by activation of AMPK and suppression of akt

Creator:

Badi, R. M., Khaleel, E. F., El-Bidawy, M. H., Satti, H. H., and Mostafa, D. G.

Identifier:

https://cdk.lib.cas.cz/client/handle/uuid:a2414a0c-c5b3-47fb-bf64-d6c2a65b636d
uuid:a2414a0c-c5b3-47fb-bf64-d6c2a65b636d

Subject:

Exendin-4, ovarian cancer, autophagy, AMPK, PI3K, Akt, and mTORC1

Type:

model:article and TEXT

Format:

bez média and svazek

Description:

Activation of autophagy suppresses ovarian cancer (OC). This in vitro study investigated whether the anti-tumour effect of exendin-4 against OC involves modulation of autophagy and figured out the possible mechanisms of action. SKOV-3 and OVCAR-3 cells (1 × 105/ml) were cultured in DMEM medium and treated with exendin-4 in the presence or absence of chloroquine (CQ), an autophagy inhibitor. In some cases, cells were also treated with exendin- 4 with or without pre-treatment with compound C (CC), an AMPK inhibitor, or insulin-like growth factor (IGF-1), a PI3K/Akt activator. Exendin-4 increased expression of beclin-1 and LC3I/II, suppressed expression of p62, reduced cell survival, migration, and invasion, and increased cell apoptosis and LDH release in both SKOV-3 and OVCAR-3 cells. Besides, exendin-4 reduced phosphorylation of mTORC1, 6SK, 4E-BP1, and Akt but increased phosphorylation of AMPK in both cell lines. These effects were associated with down-regulation of Bcl-2, suppression of nuclear phosphorylation of NF-κB p65, and increased expression of Bax and cleaved caspases 3/8. Chloroquine completely prevented the inhibitory effects of exendin-4 on the cell survival, Bcl-2, NF-κB, and cell invasiveness and abolished its stimulation of cell apoptosis and LDH release. Moreover, only the combined treatment with IGF-1 and CC completely abolished the observed effect of exendin-4 on the expression of beclin-1, LC3I/II, p62, as well as on cell survival, apoptosis, and LDH release. Exendin-4 exhibits a potent anti-tumour cytotoxic effect in SKOV-3 and OVCAR-3 cells by activating the markers of autophagy, mediated by activation of AMPK and inhibition of Akt.

Language:

English

Rights:

http://creativecommons.org/publicdomain/mark/1.0/
policy:public

Coverage:

186-203

Source:

Folia biologica | 2020 Volume:66 | Number:5-6

Harvested from:

CDK

Metadata only:

false