Auranofin is a gold-containing drug used to alleviate the symptoms of rheumatoid arthritis.
A novel treatment approach combining the anti-cancer drug RAPTA-T with a rheumatoid arthritis (RA) drug called auranofin (Ridaura) improved the efficacy of the former drug’s cancer-killing ability.
In a study published in Nature Communications, the investigators sought to explore the synergistic effects of the 2 unrelated drugs. Auranofin is a gold-containing drug used to alleviate RA symptoms.
RAPTA-T is a ruthenium-containing anticancer drug designed to disrupt tumor growth and metastasis, while reducing the adverse events of chemotherapy. Although auranofin is used to treat RA, recent studies show it also exhibits activity against cancer.
For the study, the investigators examined the synergistic effects of RAPTA-T and auranofin on packaged DNA inside cancer cells. They found that together, the drugs increased the efficacy of killing cancer cells, while individually, the drugs had significantly less of an impact on cell viability.
When RAPTA-T is administered, it forms adducts with the histone proteins that package DNA, which disrupts the DNA’s normal function, causing the cell to die. Contrastingly, auranofin is less prone to form adducts with the histone proteins unless the 2 drugs are used in combination.
The results of the study showed that the binding of auranofin takes place through an allosteric action-over-a-distance mechanism within the nucleosome, which contains the cell’s packaged DNA. RAPTA-T helps the other drug’s ability to form histone adducts by binding on distant histone sites.
The findings suggest that “allosteric modulation in nucleosomes may have biological relevance and potential for therapeutic interventions,” the authors concluded.