A novel anti-cancer effect of genistein: reversal of epithelial mesenchymal transition in prostate cancer cells.
OBJECTIVE
The aim of the present study was to investigate whether low dose genistein affects the invasion and epithelial mesenchymal transition (EMT) of prostate cancer (PCa) cells.


METHODS
Human PCa cell lines, IA8-ARCaP and LNCaP/ HIF-1a, were used in this study. The cell lines were found to process EMT in our previous study. The PCa cells were treated with increasing concentrations, from 0.1 to 75 micromol/L. Proliferation was assessed with 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide assay. EMT was proven by cell morphological transition and the expression changes of EMT-related markers, which were confirmed by RT-PCR, Western blotting, and indirect immunofluorescence labeling. Transwell invasion assay was used to analyze the invasive potency.


RESULTS
The addition of genistein to the medium reduced the IA8-ARCaP and LNCaP/HIF-1a viable cell number in a dose-dependent manner (with increasing concentrations from 15 to 75 micromol/L). Less than 15 micromol/L genistein was selected as the low dose concentration, which did not affect cell proliferation. The treatment of cells with low-dose genistein induced the reversal of EMT, which was confirmed by cell morphological transition and the expression changes of EMT-related markers. The reversal of EMT in the PCa cells by low-dose genistein was in a dose-dependent manner. Moreover, low-dose genistein effectively inhibited invasion of the PCa cells in vitro.


CONCLUSIONS
These results showed that treatment with low-dose genistein may be a potential strategy for the suppression of invasive growth through the reversal of EMT in cancer cells, which justifies the potential use of soybean foods as a practical chemopreventive approach for patients with PCa.
Zhang
Lin-lin
LL
Department of Urology, First Affiliated Hospital of Medical School, Xioan Jiaotong University, Xioan 710061, China.
Li
Lei
L
Wu
Da-peng
DP
Fan
Jin-hai
JH
Li
Xiang
X
Wu
Kai-jie
KJ
Wang
Xin-yang
XY
He
Da-lin
DL
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects*; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness / Q000473:pathology; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000517:prevention & control*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013778:Tetrazolium Salts; D013844:Thiazoles
D016588:Anticarcinogenic Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; D019833:Genistein; C022616:thiazolyl blue