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

Acta Pharmacol Sin. 2007 Mar;28(3):446-52. doi: 10.1111/j.1745-7254.2007.00536.x.

Abstract

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 kappaB (NF-kappaB) 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-kappaB protein level and the NF-kappaB signal pathway. The expression of genes involved in the NF-kappaB signal pathway, including cyclin D1, inhibitors of kappaBs (I kappaB alpha), and phosphorylated Akt (p-AKT), were measured. In addition, transient transfection assays with the 5X NF-kappaB 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-kappaB activity in the PC-3 cells. The expression of cyclin D1, a crucial cell cycle regulator and an NF-kappaB 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-kappaB activity and the NF-kappaB signal pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgens / physiology
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Cell Nucleus / chemistry
  • Cell Nucleus / metabolism
  • Cell Proliferation / drug effects
  • Cyclin D1 / biosynthesis
  • Cyclin D1 / genetics
  • Humans
  • Male
  • Mastic Resin
  • NF-kappa B / drug effects*
  • Oncogene Protein v-akt / biosynthesis
  • Oncogene Protein v-akt / genetics
  • Prostatic Neoplasms / drug therapy*
  • Resins, Plant / pharmacology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects

Substances

  • Androgens
  • Antineoplastic Agents, Phytogenic
  • Mastic Resin
  • NF-kappa B
  • Resins, Plant
  • Cyclin D1
  • Oncogene Protein v-akt