title: Ginsenoside Rg3 inhibits colorectal tumor growth through the down-regulation of Wnt/ß-catenin signaling.
abstract: Colorectal cancer (CRC) is one of the most common and deadly malignancies in the world. Most CRCs are initiated by aberrant activation of the Wnt/ß-catenin signaling pathway. Despite the advances in its early diagnosis, optimized surgical approaches, and chemotherapies, the clinical management of advanced CRC requires effective adjuvant agents. Ginsenoside Rg3 is a single compound isolated from American ginseng (Panax quinquefolius L., Araliaceae) and Asian ginseng (Panax ginseng C. A. Meyer). We investigated the anticancer activity of Rg3 on colon cancer cells and its potential molecular mechanism behind Rg3's anticancer activity. We found that Rg3 inhibits cell proliferation and viability of cancer cells in vitro. This inhibitory effect of Rg3 is, at least in part, mediated by blocking nuclear translocation of the ß-catenin protein and hence inhibiting ß-catenin/Tcf transcriptional activity. Allelic deletion of the oncogenic ß-catenin in HCT116 cells renders the cells more sensitive to Rg3-induced growth inhibition. Using the xenograft tumor model of human colon cancer, we have demonstrated that Rg3 effectively inhibits the growth of tumors derived from the human colon cancer cell line HCT116. Histologic examination revealed that Rg3 inhibits cancer cell proliferation, decreases PNCA expression and diminishes nuclear staining intensity of ß-catenin. Taken together, our results strongly suggest that the anticancer activity of Rg3 may be in part caused by blocking the nuclear translocation of ß-catenin in colon cancer cells. This line of investigation may lead to the development of novel therapies in which Rg3 can be used as an effective adjuvant agent for the clinical management of colorectal cancers.
authors.affiliation: Department of Pharmacology and the Key Laboratory of Diagnostic Medicine designated by Chinese Ministry of Education, Chongqing Medical University, Chongqing, PR China.
authors.forename: Bai-Cheng
authors.initials: BC
authors.lastname: He
authors.forename: Jian-Li
authors.initials: JL
authors.lastname: Gao
authors.forename: Xiaoji
authors.initials: X
authors.lastname: Luo
authors.forename: Jinyong
authors.initials: J
authors.lastname: Luo
authors.forename: Jikun
authors.initials: J
authors.lastname: Shen
authors.forename: Linyuan
authors.initials: L
authors.lastname: Wang
authors.forename: Qixin
authors.initials: Q
authors.lastname: Zhou
authors.forename: Yi-Tao
authors.initials: YT
authors.lastname: Wang
authors.forename: Hue H
authors.initials: HH
authors.lastname: Luu
authors.forename: Rex C
authors.initials: RC
authors.lastname: Haydon
authors.forename: Chong-Zhi
authors.initials: CZ
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Du
authors.forename: Chun-Su
authors.initials: CS
authors.lastname: Yuan
authors.forename: Tong-Chuan
authors.initials: TC
authors.lastname: He
authors.forename: Bing-Qiang
authors.initials: BQ
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects*; D003114:Colony-Forming Units Assay; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation; D005260:Female; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D036145:Ginsenosides / Q000494:pharmacology*; D006801:Humans; D007124:Immunoenzyme Techniques; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D005894:Panax; D015398:Signal Transduction / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D036145:Ginsenosides; D051153:Wnt Proteins; D051176:beta Catenin; C097367:ginsenoside Rg3; D008156:Luciferases