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

Abstract Background Melanoma, the most aggressive and lethal form of skin cancer, accounts for only 4% of all skin malignancies but is responsible for 80% of all skin cancer-related deaths. This study aimed to investigate the safety and antitumor efficacy of the total leaf extract of Annona muricata Linn (AME) in a melanoma model in Swiss albino mice. Materials and methods The safety of AME was evaluated by testing the acute toxicity of AME in healthy mice. Melanoma tumors were induced by subcutaneous implantation of the B16F10 murine melanoma cell line into either immunocompetent or immunodeficient Swiss albino mice via cyclophosphamide. B16F10-innoculated mice were treated with AME either by oral administration at a dose of 200 mg/kg, by topical application at a concentration of 20 mg/mL or by a combination of oral (100 mg/kg) and topical (10 mg/mL) treatment. Tumor progression was monitored throughout the experiment by measuring tumor size weekly. At the end of the experiment, histological analysis of excised tumor tissues was performed. Results The estimated LD50 of AME was approximately 2180.28 ± 84.76 mg/kg. The implantation of B16F10 cells into immunodeficient Swiss albino mice resulted in the development of solid tumors the day after implantation. The tumor size increased gradually, reaching its peak at week 3. Histological analysis revealed aggressive invasion of tumor cells into skeletal muscle and neural structures. Compared with no treatment, AME treatment significantly inhibited tumor growth (p < 0.01), whereas the combination of oral and topical treatments resulted in the lowest average tumor volume with a moderate invasion profile. Conclusion AME was slightly hazardous to Swiss albino mice. This extract exhibited antimelanoma effects by inhibiting tumor growth and progression when administered orally, when applied topically, and especially when used in combination. These findings support the potential of AME as a complementary therapeutic agent for melanoma treatment.