Cinnamophilin ameliorates testosterone-induced prostatic hyperplasia and fibrosis by regulating 5α-reductase and TGF-β/Smad signaling pathway.

OBJECTIVES

Androgen and TGF-β1/Smad signaling pathways play important roles in epithelial-mesenchymal transition (EMT), fibrosis, and the development of benign prostatic hyperplasia (BPH). Cinnamophilin is extracted from Cinnamomum philippinense. The anti-proliferative and anti-fibrosis effects of cinnamophilin on the prostate remain unclear. This study aimed to investigate the therapeutic effects and molecular mechanism of action of cinnamophilin on prostate growth in testosterone propionate (TP)-treated mice.

MATERIALS AND

METHODS

The study was conducted both in vivo and in vitro. TP was injected subcutaneously to induce prostate enlargement and growth. Cinnamophilin (40 mg/kg) was orally administered once a day in TP (7.5 mg/ kg)-treated mice for 28 days. The morphological characteristics and fibrosis of the prostate were examined by H&E (Hematoxylin and Eosin) and Masson's trichrome stain. Protein expression was determined by Western blot. BPH-1 and WPMY-1 cells were treated with different concentrations of cinnamophilin (1-100 μM).

RESULTS

Cinnamophilin (40 mg/kg) significantly reduced prostate weight and prostate index in animal models. Cinnamophilin inhibited the protein expression of 5α-reductase type II and prostate-specific antigen (PSA) in TP-treated mice. Cinnamophilin reversed morphological changes, EMT, and fibrosis in TP-treated mice. Cinnamophilin increased E-cadherin but decreased N-cadherin, vimentin, fibronectin, α-SMA, TGFBR2, TGF-β1, p-Smad2/3, collagen I, collagen III, and collagen IV protein expressions. The expression of Smad2/3 was not significantly different among these groups. Cinnamophilin (100 μM) inhibited proliferation at 48 hr in BPH-1 and WPMY-1 cells.

CONCLUSION

These findings suggest that cinnamophilin inhibits prostate growth and mitigates EMT and fibrosis by regulating TGFβ/Smad signaling pathways.