title: Potent anti-metastatic activity of dimeric sesquiterpene thioalkaloids from the rhizome of Nuphar pumilum.
abstract: The methanolic extract and its alkaloid fraction from the rhizomes of Nuphar pumilum inhibited invasion of B16 melanoma cells across collagen-coated filters in vitro. Dimeric sesquiterpene thioalkaloids with the 6-hydroxyl group, 6-hydroxythiobinupharidine, 6,6'-dihydroxythiobinupharidine, and 6-hydroxythionuphlutine B, showed potent activity with IC(50) values of 0.029, 0.087, and 0.36 microM, respectively, but dimeric sesquiterpene thioalkaloids lacking the 6-hydroxyl group (thiobinupharidine, neothiobinupharidine, syn-thiobinupharidine sulfoxide, thionuphultine B beta-sulfoxide, and neothiobinupharidine beta-sulfoxide) and monomeric sesquiterpene alkaloids (nupharidine, deoxynupharidine, 7-epideoxynupharidine, and nupharolutine) showed weak activity. The alkaloid fraction (20 mg/kg/d, po) and the principal dimeric sesquiterpene thioalkaloid 6-hydroxythiobinupharidine (5 mg/kg/d, po) significantly inhibited lung tumor formation by more than 90% 10 days after injection of B16 melanoma cells in mice.
authors.affiliation: Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8412, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Matsuda
authors.forename: Toshio
authors.initials: T
authors.lastname: Morikawa
authors.forename: Mamiko
authors.initials: M
authors.lastname: Oda
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Asao
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yoshikawa
mesh_terms: D000470:Alkaloids / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification*; D019281:Dimerization; D005260:Female; D008175:Lung Neoplasms / Q000473:pathology / Q000517:prevention & control / Q000556:secondary; D008546:Melanoma, Experimental / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D008958:Models, Molecular; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D031654:Nuphar; D027343:Rhizome; D012717:Sesquiterpenes / Q000302:isolation & purification* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000470:Alkaloids; D000970:Antineoplastic Agents; D012717:Sesquiterpenes