Cytostatic activity of aeroplysinin-1 against lymphoma and epithelioma cells.

Abstract

(+/-)-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.

• Authors: M H Kreuter, A Bernd, H Holzmann, W Müller-Klieser, A Maidhof, N Weissmann, Z Kljajić, R Batel, H C Schröder, W E Müller
• Journal: Zeitschrift fur Naturforschung. C, Journal of biosciences (Z Naturforsch C J Biosci) 1989 Jul-Aug Vol. 44 Issue 7-8 Pg. 680-8 ISSN: 0939-5075 [Print] Germany
• PMID: 2673260 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Acetonitriles
• Antineoplastic Agents
• Cyclohexenes
• aeroplysinin I

Topics

• Acetonitriles (pharmacology, therapeutic use)
• Animals
• Antineoplastic Agents (pharmacology)
• Carcinoma
• Cell Line
• Cell Survival (drug effects)
• Cyclohexenes
• Drug Screening Assays, Antitumor
• Humans
• Leukemia L5178 (drug therapy)
• Leukemia, Experimental (drug therapy)
• Male
• Mice
• Mice, Inbred Strains
• Mutagenicity Tests
• Salmonella typhimurium (drug effects)
• Tumor Cells, Cultured (cytology, drug effects)