Cytostatic activity of aeroplysinin-1 against lymphoma and epithelioma cells.
(+/-)-Aeroplysinin-1, an optically active 1,2-dihydroarene-1,2-diol, was isolated from the marine sponges Verongia aerophoba (+-isomer) and Ianthella ardis (- -isomer). For the experiments presented we used the +-isomer from Verongia aerophoba. Here we describe the hitherto unknown biological and pharmacological property of this compound to display pronounced anticancer activity against L5178y mouse lymphoma cells (ED50: 0.5 microM). Friend erythroleukemia cells (ED50: 0.7 microM), human mamma carcinoma cells (ED50: 0.3 microM) and human colon carcinoma cells (ED50: 3.0 microM) in vitro. Furthermore, aeroplysinin caused a preferential inhibition of [3H]thymidine (dThd) incorporation rates in L5178y mouse lymphoma cells if compared with murine spleen lymphocytes in vitro. At concentrations between 1.1 and 28.5 microM, the [3H]dThd incorporation rates in L5178y cells were suppressed to 28%-0% but only to 78%-18% in murine spleen lymphocytes. The same differential effect in vitro was found with the following epithelial cells: 14.70 microM of the compound were required to inhibit normal human fibroblasts to 50%, but only 2.9 microM in the assays with human malign keratinocytes or malignant melanoma cells to observe the same inhibitory effect. Moreover, aeroplysinin-1 displayed antileukemic activity in vivo using the L5178y cell/NMRI mouse system; administered at a dose of 50 mg/kg for five consecutive days, the T/C (%) value was determined to be 338. Preliminary toxicology studies revealed an acute LD50 of 202 mg/kg and a subacute LD50 of 150 mg/kg. Aeroplysinin-1 is neither a direct mutagen nor a premutagen in the umu/Salmonella typhimurium test system.
Kreuter
M H
MH
Abteilung Angewandte Molekularbiologie, Universität, Mainz, Bundesrepublik Deutschland.
Bernd
A
A
Holzmann
H
H
Müller-Klieser
W
W
Maidhof
A
A
Weissmann
N
N
Kljajić
Z
Z
Batel
R
R
Schröder
H C
HC
Müller
W E
WE
D000097:Acetonitriles / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002277:Carcinoma; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D053138:Cyclohexenes; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007940:Leukemia L5178 / Q000188:drug therapy*; D007942:Leukemia, Experimental / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009152:Mutagenicity Tests; D012486:Salmonella typhimurium / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000166:cytology* / Q000187:drug effects
D000097:Acetonitriles; D000970:Antineoplastic Agents; D053138:Cyclohexenes; C042151:aeroplysinin I