The anti‐tumourigenic effect of ellagic acid in SKOV‐3 ovarian cancer cells entails activation of autophagy mediated by inhibiting Akt and activating AMPK
| Autor: | Mohamed A. Alshehri, Ali S. Alsheri, Ehab El Sayed Massoud, Fahmy G. Elsaid, Haitham I. El‐Mekkawy, Amira M. Al‐Ramlawy, Ali A. Shati, Mohamed E. Abdraboh, Attalla F. El-kott, M.A. Al-Kahtani |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Physiology Enzyme Activators Apoptosis mTORC1 AMP-Activated Protein Kinases Mechanistic Target of Rapamycin Complex 1 03 medical and health sciences 0302 clinical medicine Ellagic Acid Cell Movement Cell Line Tumor Physiology (medical) Autophagy Humans Neoplasm Invasiveness Protein Kinase Inhibitors Protein kinase B PI3K/AKT/mTOR pathway Cell Proliferation Ovarian Neoplasms Pharmacology Cell growth Chemistry AMPK Antineoplastic Agents Phytogenic Enzyme Activation 030104 developmental biology 030220 oncology & carcinogenesis Cancer cell Cancer research Female Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | Clinical and Experimental Pharmacology and Physiology. 47:1611-1621 |
| ISSN: | 1440-1681 0305-1870 |
| DOI: | 10.1111/1440-1681.13338 |
| Popis: | 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 IC50 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 (Thr389 ) and 4EBP-1 (Thr37/46 ), two downstream targets of mTORC1, and p-Akt (Thr308 ) but increased levels of AMPK (Thr172 ) and p-raptor (Ser792 ), 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. |
| Databáze: | OpenAIRE |
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