Differential anti-proliferative and anti-migratory activities of ursolic acid, 3-O-acetylursolic acid and  their combination treatments with quercetin on melanoma cells

AlQathama, Aljawharah, Shao, Luying, Bader, Ammar, Khondkar, Proma, Gibbons, Simon and Prieto, Jose (2020) Differential anti-proliferative and anti-migratory activities of ursolic acid, 3-O-acetylursolic acid and  their combination treatments with quercetin on melanoma cells. Biomolecules, 10 (6). pp. 1-14. ISSN 2218-273X

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We evaluate how 3-acetylation modulates the in vitro activity of ursolic acid in melanoma cells alone or in combination treatments with quercetin. Anti-proliferative studies on A375 cells and adult human dermal fibroblasts included analyses on cell cycle distribution, caspase activity, phosphatidylserine translocation, cell morphology and Bax/Bcl-2 protein expression. Then, 2D and 3D migration of B16F10 cells were studied using scratch and Transwell assays, respectively. Ursolic acid and 3-O-acetylursolic acid have shown similar GI50 on A375 cells (26 µM vs. 32 µM, respectively) significantly increased both early and late apoptotic populations, activated caspases 3/7 (48–72 h), and enhanced Bax whilst attenuating Bcl-2 expression. Ursolic acid caused elevation of the sub-G1 population whilst its 3-acetyl derivative arrested cell cycle at S phase and induced strong morphological changes. Combination treatments showed that ursolic acid and quercetin act synergistically in migration assays but not against cell proliferation. In summary, 3-O-acetylursolic acid maintains the potency and overall apoptotic mechanism of the parent molecule with a more aggressive influence on the morphology of A375 melanoma cells but the 3-acetylation suppresses its anti-migratory properties. We also found that ursolic acid can act in synergy with quercetin to reduce cell migration.

Item Type: Article
Uncontrolled Keywords: apoptosis,cell cycle,melanoma,migration,pentacyclic triterpenes,synergism,biochemistry,molecular biology ,/dk/atira/pure/subjectarea/asjc/1300/1303
Faculty \ School: Faculty of Science > School of Pharmacy
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Depositing User: LivePure Connector
Date Deposited: 17 Jun 2020 00:13
Last Modified: 22 Oct 2022 06:19
URI: https://ueaeprints.uea.ac.uk/id/eprint/75622
DOI: 10.3390/biom10060894


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