title: 2-hydroxycinnamaldehyde inhibits SW620 colon cancer cell growth through AP-1 inactivation.
abstract: 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 microg/ml, respectively. In further studies on the mechanism, we found that consistent with the inhibitory effect on cell growth, HCA dose-dependently (0-20 microg/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.
authors.affiliation: College of Pharmacy, Chungbuk National University, Korea.
authors.forename: Chung Woo
authors.initials: CW
authors.lastname: Lee
authors.forename: Seung Ho
authors.initials: SH
authors.lastname: Lee
authors.forename: Jae Woong
authors.initials: JW
authors.lastname: Lee
authors.forename: Jung Ok
authors.initials: JO
authors.lastname: Ban
authors.forename: So Yong
authors.initials: SY
authors.lastname: Lee
authors.forename: Han Soo
authors.initials: HS
authors.lastname: Yoo
authors.forename: Jae Kyung
authors.initials: JK
authors.lastname: Jung
authors.forename: Dong Cheul
authors.initials: DC
authors.lastname: Moon
authors.forename: Ki Wan
authors.initials: KW
authors.lastname: Oh
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
mesh_terms: D000171:Acrolein / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002934:Cinnamates / Q000737:chemistry / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D024202:Electrophoretic Mobility Shift Assay; D006131:Growth Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020287:In Situ Nick-End Labeling; D020128:Inhibitory Concentration 50; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D015394:Molecular Structure; D009841:Oligonucleotides / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D013329:Structure-Activity Relationship; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D002934:Cinnamates; D004268:DNA-Binding Proteins; D006131:Growth Inhibitors; D009841:Oligonucleotides; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; C117045:p-hydroxycinnamaldehyde; D000171:Acrolein; D008156:Luciferases; C012843:cinnamaldehyde