Castalin induces ROS production, leading to DNA damage and increasing the activity of CHK1 inhibitor in cancer cell lines

Background: cancer therapy is one of the challenging arguments in constant development. One of the principal problems connected with the tumor therapy arise form the potential side effects connected with the classical chemotherapeutic treatment but also with the molecular target therapy. The identification of novel molecules useful for the reduction of potential side effects but also as a new therapeutic opportunity is one of the hot topics. (2) Methods: we identified a Castalin from the chestnut shells from the NRM. We treated different cancer cell lines with Castalin alone or in combination with CHK1 inhibitor. Finally, we performed a RNaseq analysis of HeLa cells treated with Castalin. (3) Results: we demonstrated the ability of Castalin to induce DNA damage, probably by inducing an in-crease of ROS production. Consistently, the antioxidant treatment, with Ascorbic acid, re-duced the DNA damage induced with Castalin. Finally, we demonstrated the potential synergistic effect of Castalin with SRA737, a CHK1 inhibitor currently used in clinical trial (4) Conclusions: we demonstrated the ability of Castalin to induce DNA damage favoring a NHEJ repair. Moreover, the use of Castalin in combination with SRA737 increase the ef-ficacy of CHK1 inhibitor reducing its possible side effects.