WalyEldeen, Amr Ahmed  El‑Shorbagy, Haidan MHassaneen, Hamdi MAbdelhamid, Ismail ASabet, Salwa Ibrahim, Sherif Abdelaziz 2022-07-292022-07-292022-07-26https://doi.org/10.1007/s00210-022-02269-5http://repository.msa.edu.eg/xmlui/handle/123456789/5064Despite the advances made in cancer therapeutics, their adverse efects remain a major concern, putting safer therapeutic options in high demand. Since chalcones, a group of favonoids and isofavonoids, act as promising anticancer agents, we aimed to evaluate the in vivo anticancer activity of a synthetic isoquinoline chalcone (CHE) in a mice model with Ehrlich solid carcinoma. Our in vivo pilot experiments revealed that the maximum tolerated body weight-adjusted CHE dose was 428 mg/kg. Female BALB/c mice were inoculated with Ehrlich ascites carcinoma cells and randomly assigned to three dif- ferent CHE doses administered intraperitoneally (IP; 107, 214, and 321 mg/kg) twice a week for two consecutive weeks. A group injected with doxorubicin (DOX; 4 mg/kg IP) was used as a positive control. We found that in CHE-treated groups: (1) tumor weight was signifcantly decreased; (2) the total antioxidant concentration was substantially depleted in tumor tis- sues, resulting in elevated oxidative stress and DNA damage evidenced through DNA fragmentation and comet assays; (3) pro-apoptotic genes p53 and Bax, assessed via qPCR, were signifcantly upregulated. Interestingly, CHE treatment reduced immunohistochemical staining of the proliferative marker ki67, whereas BAX was increased. Notably, histopathological examination indicated that unlike DOX, CHE treatment had minimal toxicity on the liver and kidney. In conclusion, CHE exerts antitumor activity via induction of oxidative stress and DNA damage that lead to apoptosis, making CHE a promising candidate for solid tumor therapy.en-USChalcones Chemotherapy Ehrlich solid carcinoma DNA damage Oxidative stress ·ApoptosisArticlehttps://doi.org/10.1007/s00210-022-02269-5