Gambogic acid inhibits TNF-α-induced invasion of human prostate cancer PC3 cells in vitro through PI3K/Akt and NF-κB signaling pathways

Abstract

Aim: To investigate the mechanisms underlying the inhibitory effect of gambogic acid (GA) on TNF-α-induced metastasis of human prostate cancer PC3 cells in vitro. Methods: TNF-α-mediated migration and invasion of PC3 cells was examined using migration and invasion assays, respectively. NF-κB transcriptional activity and nuclear translocation were analyzed with luciferase reporter gene assays, immunofluorescence assays and Western blots. The ability of p65 to bind the promoter of Snail, an important mesenchymal molecular marker, was detected using a chromatin immunoprecipitation (ChIP) assay. After treatment with Snail-specific siRNA, the expression of invasiveness-associated genes was measured using quantitative real-time PCR and Western blot. Results: GA significantly inhibited the viability of PC3 cells at 1-5 μmol/L, but did not produce cytotoxic effect at the concentrations below 0.5 μmol/L. GA (0.125-0.5 μmol/L) dose-dependently inhibited the migration and invasion of PC3 cells induced by TNF-α (10 ng/mL). Moreover, the TNF-α-mediated activation of phosphatidylinositol-3-OH kinase/protein kinase B (PI3K/Akt) and NF-κB pathways was suppressed by GA (0.5 μmol/L). Furthermore, this anti-invasion effect of GA was associated with regulation of Snail. Snail expression was significantly down-regulated by treatment with GA (0.5 μmol/L) in the TNF-α-stimulated PC3 cells. Conclusion: GA inhibits TNF-α-induced invasion of PC3 cells via inactivation of the PI3K/Akt and NF-κB signaling pathways, which may offer a novel approach for the treatment of human prostate cancer.

17β-Estradiol Inhibites Tumor Necrosis Factor-α Induced Apoptosis of Human Nucleus Pulposus Cells via the PI3K/Akt Pathway

“…However, total Akt level remained unaltered for 48 hours. The overall trend was consistent with reports from points of Lü [44], but the peak of p-Akt occurred at 2 hours after treatment with TNF-α (10 ng/mL). The possible reasons to explain these differences are differences in concentration for TNF-α and study cells.…”

The role of Snail in prostate cancer

“…Gambogic acid (GA), a xanthonoid resin from Garcinia hurburyi tree, was able to inhibit tumor necrosis factor a (TNF-a)-induced invasion of PC3 cells in part via downregulation of Snail expression. 79 Another study has reported that the nontoxic phytochemical, silibilin, found in herbs such as milk thistle, decreased the levels of Snail and Slug, inhibited EMT and decreased migratory and invasive potential in PC3 and C4-2B prostate cancer cells. 80 Genistein, an isoflavonoid derived from soy products, when fed to transgenic adenocarcinoma mouse prostate model (TRAMP/FVB) mice, decreased the incidence of poorly differentiated cancer at the prostatic intra-epithelial neoplasia (PIN) stage.…”

Piceatannol inhibits MMP-9-dependent invasion of tumor necrosis factor-α-stimulated DU145 cells by suppressing the Akt-mediated nuclear factor-κB pathway

“…Previous studies have also identified the signal transduction pathways involved in regulating MMP-9 expression in various tumor cells (23,24). In particular, NF-κB is a significant transcription factor for regulating the MMP-9 gene promoter and contains NF-κB-binding sites (12). This study revealed that piceatannol regulates NF-κB activity by inhibiting p65 and p50 protein translocation.…”

“…A previous study demonstrated that the inhibition of NF-κB activity in human prostate cancer cells decreases their tumorigenic and metastatic abilities by suppressing angiogenesis and invasion via the downregulation of MMP-9 (11). Conversely, TNF-α stimulation results in NF-κB activation in prostate cancer cells and induces tumor invasion (12). Therefore, a potential strategy to suppress MMP-9-mediated tumor invasion is via the NF-κB pathway.…”