The assessment of the potential anti-tumor effects of banana extract as a standalone therapy and in combination with doxorubicin in a rat model of breast cancer

Background: Breast cancer remains a leading cause of cancer-related mortality worldwide, necessitating the exploration of novel and adjunctive therapies. Owing to their low toxicity and high variety, natural products and their derivatives are becoming increasingly valuable sources for small-molecule anticancer drugs. Natural products, such as Musa sapientum (banana) extract, have shown promise in cancer research due to their bioactive compounds. This study aimed to investigate the antitumor potential of banana flesh extract (BE) alone and in combination with doxorubicin (Dox) in a DMBA-induced breast cancer rat model. Methods: Eighty female Sprague-Dawley rats were randomized into eight groups (n = 10/group): Group I (Control): Received 1% DMSO (vehicle), Group II (BE): healthy rats treated orally with BE (300 mg/kg/day), Group III (Dox): healthy rats treated with intraperitoneal Dox (2 mg/kg/week), Group IV (BE + Dox): healthy rats receiving combined BE and Dox, Group V (DMBA-induced tumor control): Untreated breast cancer rats, Group VI (Tumor + BE): DMBA-induced rats treated orally with BE (300 mg/kg/day), Group VII (Tumor + Dox): DMBA-induced rats treated with intraperitoneal Dox (2 mg/kg/week) and Group VIII (Tumor + BE + Dox): DMBA-induced rats receiving combined BE and Dox. Treatments were administered for 45 consecutive days. Histopathological analysis and molecular markers of apoptosis and cellular proliferation were evaluated in mammary tissues. Results: In DMBA-induced breast cancer rats, the combination of Dox and BE demonstrated superior anti-tumor efficacy compared to individual treatments, significantly reducing tumor size while enhancing oxidative stress mitigation (via increased SOD and catalase activity) and apoptosis (via elevated p53 and caspase-3). In healthy mammary tissue, Dox alone triggered oxidative damage and apoptosis, whereas BE—both alone and in combination—exerted a protective effect by restoring antioxidant defenses and reducing cellular injury. Histopathological findings revealed that BE alone induced mild hyperplasia in healthy tissue but countered Dox-induced atrophy, fibrosis, and inflammation. In cancerous tissue, the extract alone reduced proliferation and promoted apoptosis, while Dox caused structural disruption and fibrosis, with the combination therapy yielding the most pronounced anti-cancer effects without exacerbating normal tissue toxicity. Conclusion: BE shows potential as an adjunctive therapy to conventional chemotherapy, improving antitumor outcomes while mitigating Dox’s adverse effects. These findings support further investigation into BE’s bioactive compounds for breast cancer treatment.