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

BACKGROUND

Melanoma is an aggressive skin cancer associated with high mortality. This study evaluated the safety and antitumor efficacy of Annona muricata Linn leaf extract (AME) in a melanoma model in Swiss albino 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

The estimated LD50 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.