2-Hydroxycinnamaldehyde Inhibits SW620 Colon Cancer Cell Growth Through AP-1 Inactivation

• Published in: Journal of Pharmacological Sciences 2007, Vol.104(1), pp.19-28
• Main Authors: Lee, Chung Woo, Lee, Seung Ho, Lee, Jae Woong, Ban, Jung Ok, Lee, So Yong, Yoo, Han Soo, Jung, Jae Kyung, Moon, Dong Cheul, Oh, Ki Wan, Hong, Jin Tae
• Format: Article
• Language: English
• Subjects: 2’-hydroxycinnamaldehyde (HCA); Acrolein - analogs & derivatives; Acrolein - chemistry; Acrolein - pharmacology; AP-1; Apoptosis - drug effects; Blotting, Western; cell growth inhibition; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Cinnamates - chemistry; Cinnamates - pharmacology; colon cancer; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Dose-Response Relationship, Drug; Electrophoretic Mobility Shift Assay; Growth Inhibitors - chemistry; Growth Inhibitors - pharmacology; Humans; In Situ Nick-End Labeling; Inhibitory Concentration 50; Luciferases - genetics; Luciferases - metabolism; Molecular Structure; Oligonucleotides - genetics; Oligonucleotides - metabolism; Protein Binding; Proto-Oncogene Proteins c-fos - metabolism; Proto-Oncogene Proteins c-jun - metabolism; Structure-Activity Relationship; Transcription Factor AP-1 - genetics; Transcription Factor AP-1 - metabolism; Transfection
• ISSN: 1347-8613; 1347-8648
• DOI: 10.1254/jphs.FP0061204

Cinnamaldehyde derivatives isolated from Cinnamomum cassia have been widely used for treating dyspepsia, gastritis, and inflammatory disease as well as cancer. To investigate the anti-tumor activities of several cinnamaldehyde derivatives, we compared the inhibitory effect of cinnamaldehyde derivatives on cell growth and AP-1 transcriptional activity in SW620 human colon cancer cells since AP-1 is a transcriptional factor implicated to control cancer cell growth. Among the derivatives, 2’-hydroxycinnamaldehyde (HCA) most significantly inhibited cancer cell growth and AP-1 transcriptional activity in a dose-dependent manner with an IC50 value of 12.5 and 9 µg/ml, respectively. In further studies on the mechanism, we found that consistent with the inhibitory effect on cell growth, HCA dose-dependently (0 – 20 µg/ml) inhibited DNA binding activity of AP-1 accompanied with down regulation of c-Jun and c-Fos expressions. HCA also induced apoptotic cell death as well as expression of the apoptosis-regulating gene caspase-3, but inhibited the anti-apoptosis regulating gene bcl-2 in a dose-dependent manner. These results suggested that HCA has the most potent inhibitory effect against human colon cancer cell growth, and AP-1 may be an important target of HCA.