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

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.