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Updated: Jun 3, 2025

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Oleanolic Acid Modulates DNA Damage Response to Camptothecin Increasing Cancer Cell Death.

Giulio Mazzarotti1, Maria Cuomo1, Maria Carmen Ragosta1

  • 1Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy.

International Journal of Molecular Sciences
|January 8, 2025
PubMed
Summary

Oleanolic acid from red grape pomace alters DNA repair pathways, increasing cancer cell sensitivity to camptothecin. This natural compound enhances topoisomerase I inhibition for improved cancer treatment strategies.

Keywords:
Aglianico grape pomaceDNA damage responseDNA repairhomologous recombinationoleanolic acidsingle-strand annealing

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Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Targeting DNA damage response (DDR) pathways is crucial in cancer therapy.
  • Tumor DDR defects can lead to progression and therapy resistance.
  • Natural product extracts offer potential novel cancer treatment compounds.

Purpose of the Study:

  • Investigate oleanolic acid's (OA) role in modulating DDR.
  • Determine OA's effect on DNA repair pathway choice during camptothecin (CPT) treatment.
  • Evaluate the combined efficacy of OA and CPT in cancer cells.

Main Methods:

  • Utilized fermented Aglianico red grape pomace extract containing oleanolic acid.
  • Treated HeLa cancer cells with OA and camptothecin (CPT).
  • Assessed DNA repair pathway modulation and cell sensitivity.

Main Results:

  • Oleanolic acid shifted DNA repair from homologous recombination to single-strand annealing upon CPT treatment.
  • Combined sub-lethal OA and CPT enhanced topoisomerase I inhibition efficacy.
  • OA promoted a more mutagenic DNA repair pathway, increasing HeLa cell sensitivity.

Conclusions:

  • Oleanolic acid plays a novel role in modulating the DNA damage response.
  • OA enhances cancer cell sensitivity to topoisomerase I inhibitors like CPT.
  • OA represents a potential therapeutic agent for cancer treatment strategies.