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

Aljawharah AlQathama, Luying Shao, Ammar Bader, Proma Khondkar, Simon Gibbons, Jose Prieto

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Abstract

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.
Original languageEnglish
Article number894
Pages (from-to)1-14
Number of pages14
JournalBiomolecules
Volume10
Issue number6
DOIs
Publication statusPublished - 11 Jun 2020

Keywords

  • Apoptosis
  • Cell cycle
  • Melanoma
  • Migration
  • Pentacyclic triterpenes
  • Synergism

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