Hesperidin suppressed metastasis, angiogenesis and tumour growth in Balb/c mice model of breast cancer

Abstract

AbstractConsidering the unfavourable response of breast cancer (BC) to treatment, we assessed the therapeutic potential hesperidin in mice bearing 4T1 BC tumours. Anti‐tumour effects were assessed by measuring pathologic complete response (pCR), survival analysis, immunohistochemistry for E‐cadherin, VEGF, MMP9, MMP2 and Ki‐67, serum measurement of IFNγ and IL‐4, and gene expression analysis of CD105, VEGFa, VEGFR2 and COX2. Survival of tumour‐bearing mice was the highest in mice receiving a combination of hesperidin and doxorubicin (Dox) (80%) compared to the normal saline (43%), hesperidin 5 (54%), 10 (55.5%), 10 (60.5%) and 40 (66%) mg/kg, and 10 mg/kg Dox‐treated (73%) groups (p < 0.0001 for all). Compared to the normal saline group, there was a significant elevation in IFNγ level in the animals receiving 20 (p = 0.0026) and 40 (p < 0.001) mg/kg hesperidin, 10 mg/kg Dox (p < 0.001), and combined hesperidin (20 mg/kg) and Dox (10 mg/kg) (p < 0.001). A significant reduction in the gene expression of CD 105 (p = 0.0106), VEGFa (p < 0.0001), VEGFR2 (p < 0.0001), and Cox2 (p = 0.034) and a significant higher pCR score (p = 0.006) were noticed in mice treated with 10 mg/kg Dox + 20 mg/kg hesperidin compared to those treated with 10 mg/kg Dox alone. Immunohistochemical staining showed significant reductions in Ki‐67 (p < 0.001) and VEGF (p < 0.001) and a significant elevation in E‐cadherin (p = 0.005) in the 10 mg/kg Dox + 20 mg/kg treatment group than in 10 mg/kg Dox alone group. Hesperidin can be considered as a potentially suitable anti‐cancer agent for BC that can synergize with other chemotherapeutics.