Simvastatin ameliorates testosterone-induced prostatic hyperplasia in rats via modulating IGF-1/PI3K/AKT/FOXO signaling

El-Shafei, Nyera H.; Zaafan, Mai A.; Kandil, Esraa A.; Sayed, Rabab H.

doi:10.1016/j.ejphar.2023.175762

Cited by 3 publications

(1 citation statement)

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“…Activation of the focal adhesion kinase FAK and overexpression of focal adhesion proteins lead to abnormal adhesion of the extracellular matrix to epithelial cells [ 24 ], which is essential for the development of BPH [ 25 ]. A study showed that the PI3K/Akt signalling pathway is activated by interactions with the ECM, which participates in the cell proliferation process [ 26 , 27 ]. The activation of the PI3K signalling pathway phosphorylates AKT, increasing cell survival and decreasing apoptosis [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Avellanin A Has an Antiproliferative Effect on TP-Induced RWPE-1 Cells via the PI3K-Akt Signalling Pathway

Xu,

Cao,

Zhang

et al. 2024

Marine Drugs

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Cyclic pentapeptide compounds have garnered much attention as a drug discovery resource. This study focused on the characterization and anti-benign prostatic hyperplasia (BPH) properties of avellanin A from Aspergillus fumigatus fungus in marine sediment samples collected in the Beibu Gulf of Guangxi Province in China. The antiproliferative effect and molecular mechanism of avellanin A were explored in testosterone propionate (TP)-induced RWPE-1 cells. The transcriptome results showed that avellanin A significantly blocked the ECM–receptor interaction and suppressed the downstream PI3K-Akt signalling pathway. Molecular docking revealed that avellanin A has a good affinity for the cathepsin L protein, which is involved in the terminal degradation of extracellular matrix components. Subsequently, qRT-PCR analysis revealed that the expression of the genes COL1A1, COL1A2, COL5A2, COL6A3, MMP2, MMP9, ITGA2, and ITGB3 was significantly downregulated after avellanin A intervention. The Western blot results also confirmed that it not only reduced ITGB3 and FAK/p-FAK protein expression but also inhibited PI3K/p-PI3K and Akt/p-Akt protein expression in the PI3K-Akt signalling pathway. Furthermore, avellanin A downregulated Cyclin D1 protein expression and upregulated Bax, p21WAF1/Cip1, and p53 proapoptotic protein expression in TP-induced RWPE-1 cells, leading to cell cycle arrest and inhibition of cell proliferation. The results of this study support the use of avellanin A as a potential new drug for the treatment of BPH.

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