Geldof A A, Mastbergen S C, Henrar R E, Faircloth G T
Department of Urology/Nuclear Medicine, University Hospital, Vrije Universiteit, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands.
Cancer Chemother Pharmacol. 1999;44(4):312-8. doi: 10.1007/s002800050983.
New classes of anticancer drugs, isolated from marine organisms, have been shown to possess cytotoxic activity against multiple tumor types. Aplidine, didemnin B, and isohomohalichondrin B (IHB), among the more promising antitumor candidates, have been evaluated in the present study on a comparative basis in terms of their antiproliferative activity and neurotoxic effects in vitro.
Using a panel of different human, prostatic cancer cell lines (DU 145, PC-3 and LNCaP-FGC) the effects of Aplidine, didemnin B, and IHB on tumor cell proliferation were tested in a colorimetric (XTT) assay and compared with the effects of vincristine, vinorelbine, and Taxol. Under analogous in vitro conditions these drugs were also monitored for neurocytotoxic effects using a PC 12 cell line based model.
Didemnin B and - especially - Aplidine were more effective in the inhibition of prostate cancer cell proliferation than vincristine, vinorelbine or Taxol at concentration levels between 5 and 50 pmol/ml. At these same concentrations, however, Didemnin B and Aplidine were also most potent in the in vitro neurotoxicity assays. IHB was found to exert even more potent antiproliferative activity (at concentration levels between 0.05 and 0.1 pmol/ml). However, neurotoxic effects were also found to be present at these levels. After drug withdrawal, the neurotoxic damage, inflicted by aplidine or IHB appeared to be more long lasting than after vincristine or vinorelbine exposure.
These results point to high antiproliferative activity of aplidine and IHB in prostate cancer. At the same time, the data urge some caution in the clinical use of these agents because of potential neurotoxic side-effects. The use of a newly formulated Aplidine may involve a more favorable therapeutic profile.
从海洋生物中分离出的新型抗癌药物已显示出对多种肿瘤类型具有细胞毒性活性。在本研究中，对更有前景的抗肿瘤候选药物阿地辛、地幔素B和异高软海绵素B（IHB）在体外的抗增殖活性和神经毒性作用进行了比较评估。
使用一组不同的人前列腺癌细胞系（DU 145、PC - 3和LNCaP - FGC），通过比色法（XTT）测定法测试阿地辛、地幔素B和IHB对肿瘤细胞增殖的影响，并与长春新碱、长春瑞滨和紫杉醇的作用进行比较。在类似的体外条件下，还使用基于PC 12细胞系的模型监测这些药物的神经细胞毒性作用。
在地幔素B，尤其是阿地辛在5至50 pmol/ml的浓度水平下，比长春新碱、长春瑞滨或紫杉醇更有效地抑制前列腺癌细胞增殖。然而，在这些相同浓度下，地幔素B和阿地辛在体外神经毒性测定中也是最有效的。发现IHB具有更强的抗增殖活性（在0.05至0.1 pmol/ml的浓度水平下）。然而，在这些水平下也发现了神经毒性作用。停药后，阿地辛或IHB造成的神经毒性损伤似乎比长春新碱或长春瑞滨暴露后更持久。
这些结果表明阿地辛和IHB在前列腺癌中具有高抗增殖活性。同时，由于潜在的神经毒性副作用，这些数据提醒在临床使用这些药物时要谨慎。使用新配方的阿地辛可能具有更有利的治疗效果。
