Enhanced antitumor activity of doxorubicin by naringenin and metformin in breast carcinoma: an experimental study.

Breast cancer is the most common malignancy in women worldwide. Strategies for cancer chemotherapy commonly require the use of combination therapy for better outcomes of results. The present work is aimed to evaluate the potential of naringenin and metformin concomitant addition with doxorubicin chemotherapy against experimental breast carcinoma. The antitumor potential of drugs under the study was evaluated against methylnitrosourea (MNU)-induced breast cancer in rats and 4T1 cells-induced orthotopic breast cancer mouse model. Parameters like tumor growth, body weight, survival rate, blood glucose, hematology, and histology were determined. There was a marked reduction in tumor weight and an observed decrease in tumor multiplicity by naringenin and metformin concomitant addition with doxorubicin against MNU-induced breast carcinoma. Likewise, naringenin and metformin with doxorubicin showed a significant reduction of tumor volume and tumor weight (p < 0.01) in 4T1-induced orthotopic mouse model as compared to the same dose of doxorubicin alone, suggesting combination treatment enhanced antitumor activity in vivo. Furthermore, histology of tumor biopsies presented the improved antitumor activity of doxorubicin via increasing tumor necrosis. Hematological parameters, body weight, and survival data presented remarkable safety of combination treatment without compromising efficacy using 50% lower dose of doxorubicin as compared to the large dose of doxorubicin alone. These results demonstrate that naringenin and metformin enhanced the antitumor effect of doxorubicin in animal models of breast carcinoma, and therefore can be useful as an adjunct treatment with doxorubicin to increase its effectiveness at the lower dose level for the treatment of cancer.