title: Triterpenoids from the floral spikes of Betula platyphylla var. japonica and their reversing activity against multidrug-resistant cancer cells.
abstract: Four new triterpenes, together with 16 known triterpenes, were isolated from the floral spikes of Betula platyphylla var. japonica in a search for compounds capable of reversing multidrug resistance in cancer cells. The structures of the new triterpenes were elucidated as 3,4-seco-olean-4(23),13(18)-dien-3-oic acid (1), 3,4-seco-urs-4(23),20(30)-dien-3-oic acid (2), 3-O-methylmalonylepiocotillol II (6), and 3-O-methylmalonylcabraleahydroxylactone (16) by spectroscopic examination. The cytotoxicity of the isolated triterpenes against human cancer cell lines as well as multidrug-resistant cancer cell lines was evaluated. Most of the isolated triterpenes showed very weak cellular toxicities. Although no discernible differences were found in the cytotoxicities for the tested compounds against sensitive and resistant cell lines, the cytotoxicities for several triterpenes against multidrug-resistant cancer cell lines (KB-C2 or K562/Adr) were enhanced in the presence of nontoxic concentrations of colchicine or doxorubicin. Compound 10 reversed the cytotoxicity of colchicine against KB-C2 cells at 8.1 microM and showed comparable potency to 5 microM verapamil.
authors.affiliation: Graduate School of Pharmaceutical Sciences, University of Tokushima, Shomachi 1-78, Tokushima 770-8505, Japan. kasiwada@ph.tokushima-u.ac.jp
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Kashiwada
authors.forename: Michiko
authors.initials: M
authors.lastname: Sekiya
authors.forename: Kimihisa
authors.initials: K
authors.lastname: Yamazaki
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Ikeshiro
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Fujioka
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamagishi
authors.forename: Shuji
authors.initials: S
authors.lastname: Kitagawa
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Takaishi
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D029662:Betula / Q000737:chemistry*; D003078:Colchicine / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007564:Japan; D007624:KB Cells; D015394:Molecular Structure; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D014315:Triterpenes; D003078:Colchicine