Inhibitory effect of caffeic acid phenethyl ester on the growth of SW480 colorectal tumor cells involves beta-catenin associated signaling pathway down-regulation.
OBJECTIVE
To study the anti-tumor effect of caffeic acid phenethyl ester (CAPE) and the influence of CAPE on beta-catenin associated signaling pathway in SW480 colorectal cancer (CRC) cells.


METHODS
SW480 cells were treated with CAPE at serial concentrations. The proliferative status of cells was measured by methabenzthiazuron (MTT) assay. Cell cycle and cell apoptosis were analyzed using flow cytometry (FCM). Western blotting assay was used to evaluate the protein level of beta-catenin, c-myc and cyclinD1. Beta-catenin localization was determined by indirect immunofluorescence.


RESULTS
CAPE displayed a strong inhibitory effect in a significant dose- and time-dependent manner on SW480 cell growth. FCM analysis showed that the ratio of G0/G1 phase cells increased, S phase ratio decreased and apoptosis rate increased after SW480 cells were exposed to CAPE for 24 h. Pretreatment of SW480 cells with CAPE significantly suppressed beta-catenin, c-myc and cyclinD1 protein expression. CAPE treatment was associated with decreased accumulation of beta-catenin protein in nucleus and cytoplasm, and concurrently increased its accumulation on the surface of cell membrane.


CONCLUSIONS
CAPE can inhibit SW480 cell proliferation by inducing cell cycle arrest and apoptosis. Decreased beta-catenin and the associated signaling pathway target gene expression may mediate the anti-tumor effects of CAPE.
He
Yu-Jun
YJ
Department of General Surgery, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China. heyujun69@yahoo.com.cn
Liu
Bao-Hua
BH
Xiang
De-Bing
DB
Qiao
Zuo-Yi
ZY
Fu
Tao
T
He
Yu-Hong
YH
D000818:Animals; D017209:Apoptosis; D002109:Caffeic Acids / Q000494:pharmacology*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D006801:Humans; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D015398:Signal Transduction; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D051176:beta Catenin / Q000378:metabolism*
D002109:Caffeic Acids; D013778:Tetrazolium Salts; D013844:Thiazoles; D051176:beta Catenin; C022616:thiazolyl blue; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol