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Repurposing Antimalarial Pyronaridine as a DNA Repair Inhibitor to Exploit the Full Potential of
Nolan Jackson1, Abdulaziz Alhussan1, Kyle Bromma1
1Department of Physics and Astronomy, University of Victoria, Victoria, BC V8P 5C2, Canada.
Pharmaceutics
|December 23, 2022
Summary
This study explored using pyronaridine (PYD) to enhance radiation therapy (RT) combined with gold nanoparticles (GNPs). The PYD/GNP/RT combination significantly increased DNA damage and reduced cancer cell proliferation, offering a promising new cancer treatment approach.
Area of Science:
- Oncology
- Radiotherapy
- Nanomedicine
Background:
- Radiation therapy (RT) is a cornerstone of cancer treatment, but normal tissue toxicity limits its effectiveness.
- Gold nanoparticles (GNPs) enhance RT efficacy by increasing radiation dose deposition in tumors.
- Inhibiting DNA repair mechanisms in cancer cells can potentiate the effects of RT.
Purpose of the Study:
- To investigate the repurposing of pyronaridine (PYD), an antimalarial drug, as a DNA repair inhibitor.
- To evaluate the combined efficacy of PYD, GNPs, and RT in enhancing DNA damage and reducing proliferation in cancer cell lines.
Main Methods:
- Cancer cell lines (HeLa and HCT-116) were treated with pyronaridine (PYD) at 500 nM.
- Cells were subsequently treated with gold nanoparticles (GNPs) and exposed to 2 Gy radiation.
- DNA double-strand breaks and cellular proliferation were quantified.
Main Results:
- PYD demonstrated significant inhibition of DNA repair at 500 nM.
- The combination of PYD, GNPs, and RT resulted in a 42% increase in DNA double-strand breaks in HeLa cells compared to GNP/RT alone.
- Combined PYD/GNP/RT treatment significantly reduced cellular proliferation in both HeLa and HCT-116 cells.
Conclusions:
- Pyronaridine acts as a DNA repair inhibitor, enhancing the DNA-damaging effects of RT/GNP treatment.
- The PYD/GNP/RT combination shows significant potential for improving cancer treatment outcomes.
- This novel approach could form the basis for future clinical translation in cancer therapy.
