Fig. 6. Effects of passion fruit extract (PFE) administration on neoplastic progression and cell cycle proteins modulation in the ventral prostate of Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) mice. (A) Representative histopathological images from TRAMP mice orally gavaged with water or PFE as described in the Materials and Methods section. Control group (CT) per 4 weeks of treatment (A1-A2): Hyperplastic secretory epithelium (Ep) (low-grade prostatic intraepithelial neoplasia, LGPIN) with folding mucosa and presence of inflammatory cells in the prostatic stroma (St) (*). A2: Highlight for LGPIN represented by more than one layer of overlapping epithelial cells presenting abundant and pale cytoplasm and prominent nuclei (arrowhead). A3: well-differentiated adenocarcinoma (WDA) (discontinuous circle) represented by the proliferation of epithelial cells towards the stromal compartment and rupture of the basement membrane. CT per 10 weeks of treatment (A3-A4): Abundant presence of pre-neoplastic lesions (high-grade prostatic intraepithelial neoplasia, HGPIN) described by the cribriform and papillary arrangement of hyperplastic epithelial cells within the acinar lumen (L). Increased fibrillar elements in prostatic St (A4) and presence of inflammatory cells (*). Passion fruit extract per 4 weeks of treatment (A5-A6): Simple secretory Ep ranging from cubic to columnar with atrophic regions (arrow). Highlight for reduction of hyperplastic epithelial cells. Passion fruit extract per 10 weeks of treatment (A7-A8): Glandular acini composed of columnar simple Ep with nuclei in the basal position. Some remnants of LGPIN and HGPIN type lesions are noted. Prostatic St with regular appearance (H&E, × 400, scale bar: 50 µm). (B) Relative frequency of different morphological features found in the ventral prostate of TRAMP mice (n = 5 per group). The results are expressed as mean ± SD. Significantly different (*P < 0.05; **P < 0.01; ***P < 0.001). (C) Representative immunoblots from all experimental groups. Ventral prostate lysates (n = 5) from all experimental groups were submitted to Western blotting for cyclin-dependent kinase 4 (cdk4), cyclin D1, p21, and β-actin. The numbers on top of the band indicate fold change in protein level compared to corresponding water-treated control TRAMP mice. β-actin was used for normalization.

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