title: Antitumor activity of 2-hydroxycinnamaldehyde for human colon cancer cells through suppression of β-catenin signaling.
abstract: The antiproliferative and antitumor activities of 2-hydroxycinnamaldehyde (1), a phenylpropanoid isolated from the bark of Cinnamomum cassia, were investigated using human colorectal cancer cells. Compound 1 exhibited antiproliferative effects in HCT116 colon cancer cells, accompanied by modulation of the Wnt/β-catenin cell signaling pathway. This substance was found also to inhibit β-catenin/T-cell factor (TCF) transcriptional activity in HEK293 cells and HCT116 colon cancer cells. Further mechanistic investigations in human colon cancer cells with aberrantly activated Wnt/β-catenin signaling showed that 1 significantly suppressed the binding of β-catenin/TCF complexes to their specific genomic targets in the nucleus and led to the down-regulation of Wnt target genes such as c-myc and cyclin D1. In an in vivo xenograft model, the intraperitoneal administration of 1 (10 or 20 mg/kg body weight, three times/week) for four weeks suppressed tumor growth in athymic nude mice implanted with HCT116 colon cancer cells significantly, without any apparent toxicity. In an ex vivo biochemical analysis of the tumors, compound 1 was also found to suppress Wnt target genes associated with tumor growth including β-catenin, c-myc, cyclin D1, and survivin. The suppression of the Wnt/β-catenin signaling pathway is a plausible mechanism of action underlying the antiproliferative and antitumor activity of 1 in human colorectal cancer cells.
authors.affiliation: College of Pharmacy, Natural Products Research Institute, Seoul National University, Seoul 151-742, Korea.
authors.forename: Min Ai
authors.initials: MA
authors.lastname: Lee
authors.forename: Hyen Joo
authors.initials: HJ
authors.lastname: Park
authors.forename: Hwa-Jin
authors.initials: HJ
authors.lastname: Chung
authors.forename: Won Kyung
authors.initials: WK
authors.lastname: Kim
authors.forename: Sang Kook
authors.initials: SK
authors.lastname: Lee
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002934:Cinnamates / Q000737:chemistry / Q000494:pharmacology*; D032904:Cinnamomum aromaticum / Q000737:chemistry; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019938:Cyclin D1 / Q000378:metabolism; D045325:HCT116 Cells; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D024301:Plant Bark / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects; D051820:TCF Transcription Factors / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects; D051176:beta Catenin / Q000235:genetics / Q000502:physiology
chemical_list: D000970:Antineoplastic Agents; D002934:Cinnamates; D051820:TCF Transcription Factors; D051176:beta Catenin; C117045:p-hydroxycinnamaldehyde; D019938:Cyclin D1