Cytostatic Activity of Aeroplysinin-1 against Lymphoma and Epithelioma Cells

Abstract

(±)-A eroplysinin-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 experim ents 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 erythroleukem ia cells (ED50: 0.7 μm), human mamma carcinoma cells (ED50: 0.3 μm) and human colon carcinoma cells (ED50: 3.0 μm) in vitro. Furtherm ore, 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 m elanoma 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 prem utagen in the umulSalmonella typhimurium test system. © 1989, Walter de Gruyter. All rights reserved.