Lignans inhibit cell growth via regulation of Wnt/beta-catenin signaling.
As aberrant activation of Wnt/beta-catenin signaling is one of the major mechanisms of carcinogenesis in colon cancer, identification of inhibitors of this pathway may aid in colon cancer prevention. We investigated the ability of the lignans arctiin, matairesinol and arctigenin from Saussurea salicifolia to inhibit Wnt/beta-catenin signaling in SW480 human colon cancer cells. The lignans inhibited SW480 cell growth. In addition, the transcriptional activity of a reporter construct containing the TCF binding element (TBE) was decreased after the treatment with all three lignans. Although arctiin, matairesinol and arctigenin have similar structures, arctigenin affected Wnt/beta-catenin signaling most significantly. Further, arctigenin reduced the level of beta-catenin by inducing its phosphorylation and thus its degradation. Arctigenin also decreased expression of the beta-catenin/TCF downstream genes CCND1, survivin and CTNNB1, and induced apoptosis. These results suggest that arctigenin, an aglycone with a methoxyl group, potently inhibits the growth of human colon cancer cells via the Wnt/beta-catenin signaling pathway.
Natural Products Research Center, Korea Institute of Science and Technology, Gangneung, Gangwon-do 210-340, Republic of Korea.
Ji-Hye
JH
Yoo
Hee Ju
HJ
Lee
Kyungsu
K
Kang
Eun Hye
EH
Jho
Chul Young
CY
Kim
Dulamjav
D
Baturen
Jigjidsuren
J
Tunsag
Chu Won
CW
Nho
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D005663:Furans / Q000737:chemistry / Q000494:pharmacology; D005960:Glucosides / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007202:Indicators and Reagents; D017705:Lignans / Q000737:chemistry / Q000494:pharmacology; D008031:Lignin / Q000737:chemistry / Q000494:pharmacology*; D010766:Phosphorylation; D012334:RNA, Neoplasm / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D030441:Saussurea / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects; D051153:Wnt Proteins / Q000502:physiology*; D051176:beta Catenin / Q000502:physiology*
D000972:Antineoplastic Agents, Phytogenic; D005663:Furans; D005960:Glucosides; D007202:Indicators and Reagents; D017705:Lignans; D012334:RNA, Neoplasm; D051153:Wnt Proteins; D051176:beta Catenin; C068935:matairesinol; D008031:Lignin; C077992:arctiin; C071942:arctigenin