Mechanisms of antiprostate cancer by gum mastic:: NF-κB signal as target

Aim: To study the effect of gum mastic, a natural resin, on the proliferation of androgen-independent prostate cancer PC-3 cells, and further investigate the mechanisms involved in this regulatory system, taking nuclear factor kappa B (NF-kappa B) signal as the target. Methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and a flow cytometer were used to detect the effect of gum mastic on the proliferation of PC-3 cells. Then, reporter gene assay, RT-PCR, and Western blotting were carried out to study the effects of gum mastic on the NF-kappa B protein level and the NF-kappa B signal pathway. The expression of genes involved in the NF-kappa B signal pathway, including cyclin D1, inhibitors of kappa BS (I kappa B alpha), and phosphorylated Akt (p-AKT), were measured. In addition, transient transfection assays with the 5 x NF-kappa B consensus sequence promoter was also used to test the effects of gum mastic. Results: Gum mastic inhibited PC-3 cell growth and blocked the PC-3 cell cycle in the G1 phase. Gum mastic also suppressed NF-kappa B activity in the PC-3 cells. The expression of cyclin D1, a crucial cell cycle regulator and an NF-kappa B downstream target gene, was reduced as well. Moreover, gum mastic decreased the p-AKT protein level and increased the I kappa B alpha protein level. Conclusion: Gum mastic inhibited the proliferation and blocked the cell cycle progression in PC-3 cells by suppressing NF-kappa B activity and the NF-kappa B signal pathway.