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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