title: The hexane extract of Saussurea lappa and its active principle, dehydrocostus lactone, inhibit prostate cancer cell migration.
abstract: Saussurea lappa has been used in Chinese traditional medicine for the treatment of abdominal pain, tenesmus, nausea, and cancer; previous studies have shown that S. lappa also induces G(2) growth arrest and apoptosis in gastric cancer cells. In this study, we investigated the effects of hexane extracts of S. lappa (HESLs) on the migration of DU145 and TRAMP-C2 prostate cancer cells. DU145 and TRAMP-C2 cells were cultured in the presence of 0-4 μg/mL HESL with or without 10 ng/mL epidermal growth factor (EGF). HESL inhibited the basal and EGF-induced migration of prostate cancer cells in a dose-dependent manner, whereas HESL did not influence the viability of these cancer cells under the conditions used in this study. Active fractions of HESL were separated via column chromatography, and the structure of the active principle was determined using (1)H and (13)C nuclear magnetic resonance spectroscopy. The active compound, dehydrocostus lactone (DHCL), in fraction 7 dose-dependently inhibited the basal and EGF-induced migration of prostate cancer cells. HESL and DHCL reduced matrix metalloproteinase (MMP)-9 and tissue inhibitor of metalloproteinase (TIMP)-1 secretion but increased TIMP-2 levels in both the absence and presence of EGF. Our results demonstrate that the inhibition of MMP-9 secretion and the stimulation of TIMP-2 secretion contribute to reduced migration of DU145 cells treated with HESL and DHCL. These results indicate that HESL containing its active principle, DHCL, has potential as an antimetastatic agent for the treatment of prostate cancer.
authors.affiliation: Center for Efficacy Assessment and Development of Functional Foods and Drugs, Hallym University, Chuncheon, Korea.
authors.forename: Eun Ji
authors.initials: EJ
authors.lastname: Kim
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Hong
authors.forename: Soon Sung
authors.initials: SS
authors.lastname: Lim
authors.forename: Gyoo Taik
authors.initials: GT
authors.lastname: Kwon
authors.forename: Jongdai
authors.initials: J
authors.lastname: Kim
authors.forename: Jong-Sang
authors.initials: JS
authors.lastname: Kim
authors.forename: Ki Won
authors.initials: KW
authors.lastname: Lee
authors.forename: Jung Han Yoon
authors.initials: JH
authors.lastname: Park
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002845:Chromatography; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006801:Humans; D007783:Lactones / Q000494:pharmacology / Q000627:therapeutic use*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D030441:Saussurea / Q000737:chemistry*; D012717:Sesquiterpenes / Q000494:pharmacology / Q000627:therapeutic use*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D007783:Lactones; D010936:Plant Extracts; D012717:Sesquiterpenes; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; C083030:dehydrocostus lactone; D004815:Epidermal Growth Factor; D020780:Matrix Metalloproteinase 9