Curcumin Induces Homologous Recombination Deficiency by BRCA2 Degradation in Breast Cancer and Normal Cells.

Background: Breast cancer (BC) is the most common cancer in women worldwide. Much progress has been made to improve treatment options for patients suffering from the disease, including a novel therapy-Poly (ADP-ribose) polymerase inhibitor (PARPi) that specifically targets tumors with deficiencies in the Homologous Recombination (HR) DNA repair pathway. To benefit better from conventional therapy, many patients seek alternative supplementation, with 20-30% of cancer patients using herbal medication on top of their regular treatment. An example of such easily available over-the-counter supplements is curcumin, a natural compound derived from turmeric (Curcuma longa). Various studies reported the potential HR deficiency (HRD) inducing effect of curcumin in cancer cells. Methods: Eight BrC and three normal cell lines and a BrC PDX model were used to evaluate the effect of curcumin on RAD51 ionizing radiation-induced focus (IRIF) formation. Three breast BrC cell lines underwent further analysis using the BRCA2 Western blot technique. To assess cell survival after treatment with curcumin and/or PARPi, a clonogenic survival assay was performed on both normal and cancerous cell lines. Results: Curcumin treatment led to a reduction in RAD51 IRIF formation capacity across all tested models. A decrease in BRCA2 levels was observed in the tested cell lines. Our findings demonstrate that HRD can be induced in both cancerous and normal cells, suggesting that curcumin treatment may increase the risk of toxicity when combined with PARPi therapy. Conclusions: The use of curcumin in combination with certain anti-cancer treatments should not be implemented without extensive monitoring for deleterious side effects.