J Biomed Res.  2015 Jun;16(2):60-66. 10.12729/jbr.2015.16.2.060.

Chemopreventive effect of alpha-viniferin in azoxymethane-induced mouse colorectal tumor and Caco-2 cells

• Kwak DH
• Shin SK
• Youm SY
• Kim TW
• Kim Y
• Ahn B

• KMID: 2286283
• DOI: http://doi.org/10.12729/jbr.2015.16.2.060

Abstract

alpha-Viniferin (AVF), a trimer of resveratrol, is known to have an anti-inflammatory effect via inhibition of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). It has been reported that up-regulated COX-2 and iNOS are expressed in colon cancer tissues of humans and rodents as well as pre-neoplastic aberrant crypt foci (ACF) of rodents. In this study, chemopreventive effects of AVF were assessed in Caco-2 cells as well as azoxymethane (AOM)-induced colorectal tumorigenesis in mice. Anti-tumor effect of AVF with regards to apoptotic induction was assessed by TUNEL and caspase-3 expression in human colon cancer Caco-2 cells. For development of ACF, AOM was administered with to mice intraperitoneally at a dose of 10 mg/kg once a week for 3 weeks. To induce colitis-related colon cancer, mice were administered a single dose of AOM (10 mg/kg) and 2% dextran sodium sulfate in drinking water. Mice treated with 0.05 and/or 0.1 mg of AVF by gavage showed significantly reduced development of ACF and colorectal tumors. Immunofluorescence detection in Caco-2 cells showed reduced COX-2 and iNOS expression, whereas cleavage of caspase-3 and apoptotic cell numbers increased upon AVF treatment. Immunostaining showed reduced expression levels of COX-2 and iNOS expression along with increased cleaved caspase-3 expression increased upon AVF treatment. These results suggest that AVF has chemopreventive effects on colorectal cancer via anti-inflammatory potential and pro-apoptotic activity.

Keyword

alpha-viniferin; Caco-2 cell; chemoprevention; colorectal cancer; mouse

MeSH Terms

Aberrant Crypt Foci
Animals
Azoxymethane
Caco-2 Cells*
Carcinogenesis
Caspase 3
Cell Count
Chemoprevention
Colonic Neoplasms
Colorectal Neoplasms*
Cyclooxygenase 2
Dextrans
Drinking Water
Fluorescent Antibody Technique
Humans
In Situ Nick-End Labeling
Mice*
Nitric Oxide Synthase Type II
Rodentia
Sodium
Azoxymethane
Caspase 3
Cyclooxygenase 2
Dextrans
Drinking Water
Nitric Oxide Synthase Type II
Sodium