Amira Ragab EL Barky1, Tarek Mostafa Mohamed1, Kamel Chaieb2,3, Bochra Kouidhi4, Ehab M. M. Ali2*
1Division of Biochemistry, Department of Chemistry, Faculty of Science, Tanta University, Tanta, Egypt
2Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia
3Center of Artificial Intelligence in Precision Medicines, King Abdulaziz University, Jeddah, Saudi Arabia
4Laboratory of Analysis, Treatment and Valorization of Pollutants of the Environmental and Products, Faculty of Pharmacy, University of Monastir, Tunisia
*Corresponding author’s email: emali@kau.edu.sa
Received: 02 January 2026 / Revised: 16 March 2026 / Accepted: 27 March 2026 / Published Online: 09 April 2026
Abstract
Dysregulation of inflammatory and antioxidant signaling is characteristic of breast cancer development and influences therapeutic efficacy. This study investigated the relationship between inflammation and cancer invasion by assessing levels and/or gene expression of COX2, Adipoq, PPARg, uPAR, sialic acid, and heparinase; apoptosis via caspase-3 evaluation; and redox balance in MCF-7 breast cancer mice treated with rutin. Three groups of virgin female mice were divided: (i) a control group; (ii) an MCF-7 group that was treated with Imuran before being injected with MCF-7 cells; and (iii) an MCF-7/rutin group that was given rutin (200 mg/kg). Biochemical and histological analyses were assessed after two and four weeks of post-treatment. Mice bearing breast tumors and treated with rutin exhibited less GATA-3 expression in mammary tissue at 4 weeks, signifying reduced cell invasiveness in mammary tissue at 4 weeks, Rutin therapy also resulted in decreased serum levels of prolactin, estrogen, and CA15-3 At two weeks, both untreated and rutin-treated tumor-bearing mice showed increased levels of COX2, uPAR and sialic acid, demonstrating higher inflammation and invasive potential. By four weeks, rutin-treated mice exhibited elevated serum sialic acid compared to control, but reduced compared with untreated mice, accompanied by elevated caspase-3, indicating enhanced apoptosis. Gene expression analysis revealed the upregulation of PPARg at both 2 and 4 weeks and Adipoq at 2 weeks, suggesting the activation of apoptotic pathways and adipocyte differentiation. COX2 and heparinase were downregulated at both 2- and 4-weeks reflecting suppression of inflammation and invasion. Rutin-treated mice had reduced mammary MDA and nitric oxide levels at 2 and 4 weeks while mammary GSH and catalase activity were elevated at 2 weeks and depleted at 4 weeks in comparison to healthy mice. It was concluded that rutin treatment of mice bearing breast cancer improved oxidative balance, modulated inflammation, reduced invasion, and preserved mammary tissue structure in breast cancer-induced mice. It is recommended to study the treatment of mice with breast cancer or other types of cancer with chemotherapy combined with rutin to mitigate the side effects of these drugs.
Keywords: Rutin, Tumor breast markers, GATA-3, COX-2, Heparinase, PPARg, Adipoq, NO, ROS
