Potent anti-metastatic activity of dimeric sesquiterpene thioalkaloids from the rhizome of Nuphar pumilum.
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.
Matsuda
Hisashi
H
Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8412, Japan.
Morikawa
Toshio
T
Oda
Mamiko
M
Asao
Yasunobu
Y
Yoshikawa
Masayuki
M
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
D000470:Alkaloids; D000970:Antineoplastic Agents; D012717:Sesquiterpenes