Effect of caffeic acid phenethyl ester on proliferation and apoptosis of colorectal cancer cells in vitro.
OBJECTIVE
To study the effect of caffeic acid phenethyl ester (CAPE) on proliferation, cell cycle, apoptosis and expression of beta-catenin in cultured human colorectal cancer (CRC) cell line HCT116.


METHODS
HCT116 cells were treated with CAPE at serial concentrations of 80, 40, 20, 10, 5, 2.5 mg/L. The proliferative status of HCT116 cells was measured by using methabenzthiazuron (MTT) assay. Cell cycle was analyzed by using flow cytometry (FCM) with propidium iodide (PI) labeling method. The rate of apoptosis was detected by using FCM with annexin V-FITC and PI double labeling method. beta-catenin levels were determined by Western blotting. beta-catenin localization in HCT116 was determined by indirect immunofluorescence.


RESULTS
After HCT116 cells were exposed to CAPE (80, 40, 20, 10, 5, and 2.5 mg/L) for 24, 48, 72, 96 h, CAPE displayed a strong growth inhibitory effect in a dose- and time-dependent manner against HCT116 cells. FCM analysis showed that the ratio of G(0)/G(1) phase cells increased, S phase ratio decreased and apoptosis rate increased after HCT116 cells were exposed to CAPE (10, 5, and 2.5 mg/L) for 24 h. CAPE treatment was associated with decreased cytoplasmic beta-catenin, nuclear beta-catenin and a concurrent increase in beta-catenin protein expression at cell-cell junctions.


CONCLUSIONS
CAPE could inhibit HCT116 cell proliferation and induce cell cycle arrest and apoptosis. Decreased beta-catenin protein expression may mediate the anti-proliferative effects of CAPE.
Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China.
Dong
D
Wang
De-Bing
DB
Xiang
Yu-Jun
YJ
He
Zeng-Peng
ZP
Li
Xiao-Hua
XH
Wu
Jiang-Hong
JH
Mou
Hua-Liang
HL
Xiao
Qing-Hong
QH
Zhang
D017209:Apoptosis / Q000187:drug effects*; D002109:Caffeic Acids / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms; D003598:Cytoskeletal Proteins / Q000235:genetics; D006801:Humans; D015534:Trans-Activators / Q000235:genetics; D051176:beta Catenin
C495270:CTNNB1 protein, human; D002109:Caffeic Acids; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin; C032773:ethyl caffeate