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Cytostatic Activity of Aeroplysinin-1 against Lymphoma and Epithelioma Cells

Kreuter, M. H., Bernd, A., Holzmann, H., Müller-Klieser, W., Maidhof, A., Weißmann, N., Kljajić, Z., Batel, R., Schröder, H. C., Müller, W.E.G.
Zeitschrift für Naturforschung 2014 v.44 no.7-8 pp. 680-688
Porifera, Salmonella Typhimurium, antineoplastic activity, colorectal neoplasms, epithelial cells, fibroblasts, humans, isomers, keratinocytes, lethal dose 50, lymphocytes, lymphoma, melanoma, mice, mutagens, neoplasm cells, spleen, thymidine, toxicology, tritium
(±)-Aeroplysinin-1, an optically active 1.2-dihydroarene-1.2-diol. was isolated from the marine sponges Verongia aerophoba (+-isomer) and lanthella 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 μm). Friend erythroleukemia cells (ED₅₀: 0.7μm) , human mamma carcinoma cells (ED₅₀: 0.3μm) and human colon carcinoma cells (ED₅₀: 3.0 μm) 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 μm, 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 μm of the compound were required to inhibit normal human fibroblasts to 50% , but only 2.9 μm 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.