Cerium oxide nanoparticles elicit antitumourigenic effect in experimental breast cancer induced by N‐methyl‐N‐nitrosourea and benzo(a)pyrene in female Wistar rats

ABSTRACT The use of cerium oxide nanoparticles [CeO2NPs] in the biomedical field has continued to gain prominence due to its potent antioxidant property. This study was designed to assess the antitumorigenic effect of CeO2NPs in rats administered N‐methyl‐N‐nitrosourea [NMU] and benzo(a)pyrene (BaP). Twenty four female Wistar rats were equally assigned into four groups and treated with normal saline (control), [NMU + BaP], [NMU + BaP+CeO2NPs], and [NMU + BaP + vincristine]. Animals were pretreated with NMU and BaP three times (age 7, 10, and 13 weeks). Thereafter, vincristine and CeO2NPs were administered twice and three times per week, respectively, for 13 weeks. Results showed that the administration of NMU and BaP increased serum nitric oxide [NO] and myeloperoxidase [MPO] by 220% and 132%, respectively, whereas the activities of aspartate and alanine aminotransferases and level of total bilirubin remained unchanged. Furthermore, mammary inflammatory [NO and MPO] and oxidative stress (LPO) markers were increased by 37%, 19%, and 24%, respectively. Mammary superoxide dismutase, catalase, reduced glutathione, and glutathione‐S‐transferase were significantly decreased in [NMU + BaP]‐administered rats by 165%, 146%, 35%, and 36%, respectively. Immunohistochemistry showed downregulation of Bax, p53, and caspase‐3, while histology revealed the presence of malignant epithelial cells with pyknotic nuclei and high nucleocytoplasm in [NMU + BaP]‐administered rats. Treatment with CeO2NPs attenuated oxidative stress, apoptosis, and inflammation and restored the cytoarchitecture of the tissue. Overall, CeO2NPs show an antitumourigenic effect in experimental breast cancer by targeting pathways linked to inflammation and apoptosis.