title: Antitumor activity of terpenoids against classical and atypical multidrug resistant cancer cells.
abstract: Nineteen terpenoids, including macrocyclic diterpenes, diterpenic lactones and other polycyclic diterpenes, steroids and a triterpene isolated from the methanolic extracts of Euphorbia species, were evaluated for their potential antineoplastic activity in various human cancer cell lines that were derived from three tumor entities: gastric (EPG85-257), pancreatic (EPP85-181) and colon (HT-29) carcinomas. Furthermore, different multidrug-resistant variants of these cancer cell lines with over-expression of MDR1/P-gp or no MDR1/P-gp expression were also investigated. In parental drug-sensitive cell lines, the tested compounds showed a moderate/weak antiproliferative effect or were inactive. Most of them were found more effective in drug-resistant cells than in the parental, drug-sensitive ones, and some of them showed high antineoplastic efficacy in classical or atypical drug-resistant cells. The most active compounds were the lathyrane diterpenes latilagascenes C and D, and the diterpenic lactones 3beta-acetoxy-helioscopinolide B and helioscopinolide E which exhibited high antineoplastic activities against the drug-resistant subline EPG85-257RDB derived from gastric carcinoma. In addition, the macrocyclic lathyrane diterpene jolkinol B was found to be highly effective in the multidrug-resistant variant HT-29RNOV.
authors.affiliation: Charité Campus Mitte, Institute of Pathology, Berlin, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Lage
authors.forename: N
authors.initials: N
authors.lastname: Duarte
authors.forename: C
authors.initials: C
authors.lastname: Coburger
authors.forename: A
authors.initials: A
authors.lastname: Hilgeroth
authors.forename: M J U
authors.initials: MJ
authors.lastname: Ferreira
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000188:drug therapy; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D028481:Euphorbia / Q000737:chemistry*; D006801:Humans; D010190:Pancreatic Neoplasms / Q000188:drug therapy; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D013274:Stomach Neoplasms / Q000188:drug therapy; D013729:Terpenes / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D013729:Terpenes