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 cytot oxic activity, Freeze-dried biological material was extracted with solvents of different polarity followed by determination of the cytotoxicity. The m ost 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 adeno carcinoma) and GLC(4) (a small cell lung carcinoma). The two cell lines wer e selected for their different response towards known cytostatics. GLC(4) i s sensitive and COLO320 is resistant to most of the known cytostatics. Thre e 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 mu g ml(-1)) than the GLC(4) (IC50:49 mu g ml(-1)). The structure is currently elucidated. Another colonial species, A plidium glabrum, yielded a very cytotoxic fraction, with an IC,, of 5 mu g 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 wit h pharmaceutical potential. (C) 1999 Elsevier Science B.V. All tights reser ved.