Antitumor potential of teriflunomide alone and in combination with vitamin D3 and tamoxifen in DMBA-induced breast cancer in BALB/c mice

Breast cancer represents a predominant malignancy which is a critical healthcare concern globally. To date, the antitumor potential of teriflunomide (Ter) in murine breast cancer models remains unexplored. Thus, the present research aimed to evaluate the potential antineoplastic efficacy of Ter in combating this fatal malignancy, alone or in combination with vitamin D 3 (Vit. D 3 ) and tamoxifen (Tam) against mammary carcinogenesis in a BALB/c mouse model induced by 7,12 dimethylbenz[a]anthracene (DMBA). BALB/c mice were divided into six groups including 7 mice each; (i) Control, (ii) DMBA, (iii) DMBA + Vit. D 3 , (iv) DMBA + Tam, (v) DMBA + Ter, and (vi) DMBA + Ter + Vit. D 3 + Tam. Results revealed that DMBA administration caused tumors with invasive ductal carcinoma of grade II and III, with a significant increase in the total microscopic score. Also, DMBA caused an increase in lipid peroxidation and a decrease in cellular antioxidants, catalase and superoxide dismutase. This was accompanied with substantial increase in expression of mutant P53. Administration of Ter individually or in combination with Vit. D 3 and Tam attenuated the development of DMBA-induced mammary tumors, and minimized the associated tissue damage, with the combination therapy demonstrating the most pronounced therapeutic impact. Our in vivo data suggest that Ter holds therapeutic potential as a promising anti-cancer candidate against breast cancer either alone or in combination with Vit. D 3 and Tam.