Therapeutic Role of Annona muricata Fruit and Bee Venom Against MNU-Induced Breast Cancer in Pregnant Rats and its Complications on the Ovaries

AIM: To evaluate the potential therapeutic role of Annona muricata (graviola) fruit and bee venom (BV) against N-methylnitrosourea (MNU)-induced breast cancer in pregnant female rats and complications in the ovaries. METHODS: A total of 24 female rats were induced with a single dose of MNU (50 mg/kg body weight). After confirmation of positive tumor marker, female rats were placed with the males for mating. The pregnant rats were randomly divided into four groups (n=6): MNU-induced only (group 1), MNU-induced rats and supplemented with A. muricata 200 mg/kg diet (group 2), MNU-induced and treated with two doses of BV 75 μg/kg (group 3), and MNU-induced and treated with both A. muricata and BV (group 4). RESULTS: In group 1, the breast tissue of mothers revealed pronounced cellular hyperplasia and histopathological signs. Also, the ovarian tissue of mothers and their offspring displayed deleterious histological changes. In groups 2 and 4, histopathological signs and cellular hyperplasia markedly disappeared in breast tissue. However, the histopathological signs induced by MNU in the ovarian tissue reversed to normal in groups 2–4. Also in groups 2–4, levels of serum MMP1, NFκB, and TNFα significantly decreased, and serum caspase 3 significantly increased either in mother rats or their offspring compared to the MNU-alone group. Levels of serum MDA significantly decreased; however, levels of serum antioxidants (CAT and SOD) significantly increased in all groups 2–4 compared to MNU-alone group. CONCLUSION: A. muricata has a more powerful therapeutic role than BV against MNU-induced breast cancer in rats; however, both have a powerful ameliorative role against ovarian histopathological alterations induced by MNU. Such ameliorative effects of A. muricata and BV are mainly attributed to their antioxidant, anti-inflammatory, and antiproliferative constituents.