The pharmaceutical exploration of cold water ascidians from the Netherlands: a possible source of new cytotoxic natural products

Six ascidian species from the Dutch North Sea coast were screened for cytotoxic activity. Freeze-dried biological material was extracted with solvents of different polarity followed by determination of the cytotoxicity. The most active extracts were further separated using different chromatographic techniques. The microculture tetrazolium (MTT) assay was used to determine the cytotoxicity against two human tumor cell lines: COLO₃₂₀ (a colon adenocarcinoma) and GLC₄ (a small cell lung carcinoma). The two cell lines were selected for their different response towards known cytostatics. GLC₄ is sensitive and COLO₃₂₀ is resistant to most of the known cytostatics. Three of the species tested yielded interesting fractions. From the in colonial Didemnum lahillei we have isolated a compound which is more active against the COLO₃₂₀ cell line (IC₅₀:33 μg ml^?1) than the GLC₄ (IC₅₀:49 μg ml^?1). The structure is currently elucidated. Another colonial species, Aplidium glabrum, yielded a very cytotoxic fraction, with an IC₅₀ of 5 μg ml^?1 against the COLO₃₂₀ cell line. From our results it can be concluded that the North Sea could be another interesting source of new compounds with pharmaceutical potential.