Department of Structural Biology, Faculty of Earth and Life Sciences, Vrije Universiteit, 1081 HV Amsterdam, The Netherlands.
Cancer Lett. 2010 Jul 28;293(2):198-206. doi: 10.1016/j.canlet.2010.01.009. Epub 2010 Feb 13.
Active small molecules have a high potential for the development into new anti-cancer drugs. Here we analysed the effect of the natural occurring fusicoccanes, Fusicoccin-A (FC), Ophiobolin-A (OPH-A) and Ophiobolin-I (OPH-I) on various tumor cell lines. Both FC and OPH-A inhibit tumor cell growth efficiently, in contrast to OPH-I. Further analysis showed that FC is tumor specific, and that its efficacy can be enhanced by combining it with the cytokine interferon-alpha (IFN-alpha). In this, IFN-alpha primes the tumor cells for apoptosis induction by FC, in which DR4 and the TRAIL pathway plays an important role. Healthy cells (HUVECs, Human Umbilical Vein Endothelial Cells) are far less sensitive to IFN-alpha/FC treatment and need the continuous presence of both compounds in order to achieve a growth reduction. This differential response between healthy and tumor cells indicates that the IFN-alpha/FC treatment is a promising new cancer treatment, especially when IFN-alpha and FC are used sequentially.
活性小分子具有开发成新型抗癌药物的巨大潜力。在这里，我们分析了天然存在的伏康酸、伏康酸-A（FC）、蛇孢菌素-A（OPH-A）和蛇孢菌素-I（OPH-I）对各种肿瘤细胞系的影响。FC 和 OPH-A 均能有效抑制肿瘤细胞生长，而 OPH-I 则不然。进一步的分析表明，FC 具有肿瘤特异性，并且通过与细胞因子干扰素-α（IFN-α）联合使用可以增强其疗效。在此过程中，IFN-α 使肿瘤细胞对 FC 诱导的细胞凋亡敏感，其中 DR4 和 TRAIL 途径发挥着重要作用。健康细胞（HUVECs，人脐静脉内皮细胞）对 IFN-α/FC 治疗的敏感性要低得多，并且需要两种化合物的持续存在才能实现生长减少。健康细胞和肿瘤细胞之间的这种差异反应表明，IFN-α/FC 治疗是一种很有前途的新型癌症治疗方法，特别是当 IFN-α 和 FC 顺序使用时。
