title: Chrysophanic acid blocks proliferation of colon cancer cells by inhibiting EGFR/mTOR pathway.
abstract: Inactivation of epidermal growth factor receptor (EGFR) is a prime method used in colon cancer therapy. Here it is shown that chrysophanic acid, a natural anthraquinone, has anticancer activity in EGFR-overexpressing SNU-C5 human colon cancer cells. Chrysophanic acid preferentially blocked proliferation in SNU-C5 cells but not in other cell lines (HT7, HT29, KM12C, SW480, HCT116 and SNU-C4) with low levels of EGFR expression. Chrysophanic acid treatment in SNU-C5 cells inhibited EGF-induced phosphorylation of EGFR and suppressed activation of downstream signaling molecules, such as AKT, extracellular signal-regulated kinase (ERK) and the mammalian target of rapamycin (mTOR)/ribosomal protein S6 kinase (p70S6K). Chrysophanic acid (80 and 120 µm) significantly blocked cell proliferation when combined with the mTOR inhibitor, rapamycin. These findings offer the first evidence of anticancer activity for chrysophanic acid via EGFR/mTOR mediated signaling transduction pathway.
authors.affiliation: Regional Cancer Institute, Chungnam National University Hospital, Daejeon 301-721, Republic of Korea.
authors.forename: Myung Sun
authors.initials: MS
authors.lastname: Lee
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Cha
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Sul
authors.forename: In Sang
authors.initials: IS
authors.lastname: Song
authors.forename: Ji Yeon
authors.initials: JY
authors.lastname: Kim
mesh_terms: D000880:Anthraquinones / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D045468:Fallopia japonica / Q000737:chemistry; D006131:Growth Inhibitors / Q000502:physiology; D006801:Humans; D051058:Oncogene Protein v-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology; D010946:Plants, Medicinal / Q000737:chemistry; D012250:Rheum / Q000737:chemistry; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000880:Anthraquinones; D000970:Antineoplastic Agents; D006131:Growth Inhibitors; D010936:Plant Extracts; D004815:Epidermal Growth Factor; C546842:MTOR protein, human; D066246:ErbB Receptors; D051058:Oncogene Protein v-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; C027113:chrysophanic acid