Investigation of the in vivo acute toxicity and antimelanoma effects of total leaf extract from Annona muricata Linn

BACKGROUND: mice. METHODS: Acute toxicity of AME was assessed in healthy mice. Melanoma was induced by subcutaneous implantation of B16-F10 cells into immunocompetent or cyclophosphamide-immunosuppressed mice. Animals received oral AME (200 mg/kg), topical AME (20 mg/mL), or a combination regimen (100 mg/kg orally + 10 mg/mL topically). Tumor progression was monitored weekly and histological analysis was performed at study completion. RESULTS: of AME was 2,180.28 ± 84.76 mg/kg. B16-F10 tumor growth was detectable from Day 1 in immunodeficient mice and peaked at Week 3. Compared with the untreated group, AME treatment reduced tumor burden and delayed progression, with the combination regimen showing the most pronounced effect (p<0.01). However, histopathological analysis revealed persistent vascular invasion and subcutaneous infiltration, indicating incomplete suppression of tumor invasiveness. CONCLUSIONS: AME demonstrated antitumor activity in this melanoma model, particularly with combined oral and topical administration. However, only a limited number of predefined dose levels were evaluated, precluding assessment of dose-response relationships and therapeutic index. These findings should be considered preliminary, and further studies are required to optimize dosing strategies and elucidate underlying mechanisms.