Caffeic acid phenethyl ester decreases cholangiocarcinoma growth by inhibition of NF‐κB and induction of apoptosis

Abstract

TXCaffeic acid phenethyl ester (CAPE) inhibits the growth of tumor cells and is a known inhibitor of nuclear factor kappa beta (NFjB), which is constitutively active in cholangiocarcinoma (CCH) cells. We evaluated the effects of CAPE on CCH growth both in vitro and in vivo. Inhibition of NF-jB DNA-binding activity was confirmed in nuclear extracts treated with CAPE at 50, 40 and 20 lM. CAPE decreases the expression of NF-jB1 (p50) and RelA (p65). CAPE decreased the growth of a number of CCH cells but not normal cholangiocytes. Cell cycle decrease was seen by a decrease in PCNA protein expression and the number of BrdUpositive cells treated with CAPE at 20 lM compared to vehicle. Inhibition of growth and increased cell cycle arrest of Mz-ChA-1 cells by CAPE were coupled with increased apoptosis. Bax expression was increased, whereas Bcl-2 was decreased in cells treated with CAPE compared to vehicle. In vivo studies were performed in BALB/c nude (nu/nu) mice implanted subcutaneously with MzChA-1 cells and treated with daily IP injections of DMSO or CAPE (10 mg/kg body weight in DMSO) for 77 days. Tumor growth was decreased and tumor latency was increased 2-fold in CAPE compared to vehicle-treated nude mice. In tumor samples, decreased CCH growth by CAPE was coupled with increased apoptosis. CAPE both in vivo and in vitro decreases the growth of CCH cells by increasing apoptosis. These results demonstrate that CAPE might be an important therapeutic tool in the treatment of CCH. ' 2009 UICC

Inhibition of Mast Cell-Derived Histamine Decreases Human Cholangiocarcinoma Growth and Differentiation via c-Kit/Stem Cell Factor–Dependent Signaling

“…13,14 Total mRNA was extracted with the Qiagen (Valencia, CA) RNeasy mini kit and, after amplification, a DDCT (D threshold cycle) analysis was performed. 15 …”

Simultaneous determination of caffeic acid phenethyl ester and its metabolite caffeic acid in dog plasma using liquid chromatography tandem mass spectrometry

“…In recent years, CAPE has attracted increasing scientific interest due to its various pharmacological activities, e.g., anticancer/tumor [2][3][4][5][6], antiviral [7,8], anti-inflammatory [9][10][11][12][13], antioxidant [14][15][16][17], cytoprotection, [18][19][20][21][22] and vasorelaxant effects [23,24]. The pharmacological effects and mechanisms of CAPE have been comprehensively reviewed recently [25].…”

Cancer Chemoprevention by Dietary Polyphenols

“…There are several studies reporting the in vitro and in vivo inhibitory ef1fects of CAPE in multiple cancer models, such as colon cancer [167], lung cancer [168], melanoma [169], glioma [170], pancreatic cancer [171], gastric cancer [172], cholangiocarcinoma [173], hepatocellular carcinoma [174], and breast cancer [175,176].…”