Annona crassiflora seed extract modulates histological and molecular markers associated with prostate cancer progression in TRAMP mice

Prostate cancer ranks second among the most common malignant neoplasms in men worldwide. Fruit extracts with potential anti-prostate cancer properties have gained increasing attention, with the most notable belonging to the Annonaceae family, including Araticum (Annona crassiflora Mart). In this study, we aimed to evaluate the chemopreventive and anti-inflammatory potential of Araticum seed extract (Annona crassiflora Mart) on the ventral prostate lobe of Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model. Sixty male TRAMP mice, aged 8 and 12 weeks, were divided into four groups: two groups received the extract at a dose of 100 mg/kg body weight, and two control groups received equivalent volumes of water and DMSO (Dimethyl Sulfoxide). After 30 days, animals were euthanized and ventral prostate samples were collected for morphological evaluation by light microscopy, immunohistochemistry, and Western blotting. Treatment with Araticum seed extract delayed the progression of premalignant and malignant lesions (HGPIN and adenocarcinoma) and preserved healthy tissue. The extract showed antiproliferative activity, reducing PCNA, IGFR-1, and AR protein levels. Inflammatory signaling was suppressed via Toll-like receptor pathways, with decreased NFκB, TNF-α, and other inflammatory markers. Moreover, the extract reduced BCL-2 expression and promoted caspase activation, suggesting pro-apoptotic protection. In conclusion, treatment with Araticum seed extract demonstrated promising chemopreventive activity, effectively reducing the progression of epithelial lesions in the ventral prostate lobe of TRAMP mice and may be suggested as a potential chemopreventive agent in combined prostate cancer therapies.