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


CONCLUSIONS
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.
He
Mei-Lan
ML
Institute of Cancer Research, Life Science and Technology School, Tongji University, Shanghai 200092, China. mmhe@mail.tongji.edu.cn
Li
Ang
A
Xu
Chun-Su
CS
Wang
Shun-Li
SL
Zhang
Meng-Jie
MJ
Gu
Hua
H
Yang
Yao-Qin
YQ
Tao
Hui-Hong
HH
D000728:Androgens / Q000502:physiology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D008297:Male; D000069997:Mastic Resin; D016328:NF-kappa B / Q000187:drug effects*; D051058:Oncogene Protein v-akt / Q000096:biosynthesis / Q000235:genetics; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D012116:Resins, Plant / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects
D000728:Androgens; D000972:Antineoplastic Agents, Phytogenic; D000069997:Mastic Resin; D016328:NF-kappa B; D012116:Resins, Plant; D019938:Cyclin D1; D051058:Oncogene Protein v-akt