Gasper Régis, Mijatovic Tatjana, Bénard Audrey, Derenne Allison, Kiss Robert, Goormaghtigh Erik
Laboratory for the Structure and Function of Biological Membranes, Center for Structural Biology and Bioinformatics, Université Libre de Bruxelles (ULB), Belgium.
Biochim Biophys Acta. 2010 Nov;1802(11):1087-94. doi: 10.1016/j.bbadis.2010.07.012. Epub 2010 Jul 22.
We show in the present work that the infrared (IR) spectrum of human PC-3 prostate cancer cells exposed to anticancer drugs could offer a unique opportunity to get a fingerprint of all the major biochemical components (DNA, RNA, proteins, lipids, etc.) present in the cells and to identify with high sensitivity the signature of the metabolic changes induced by anticancer drugs. We investigated here the FTIR-related signatures of the effect of 4 structurally-related cardiotonic steroids (CS), i.e. ouabain, 19-hydroxy-2″-oxovoruscharin, hellebrin and 19-hydroxy-hellebrin on PC-3 cancer cells incubated between 0 and 36 h in the absence (control) or the presence of the CS. For each molecule a single spectral signature described the largest part of the time dependent modifications with a possible very minor second component. The spectral signatures characterizing the effects of each of the four CS were unique but very similar when compared to the signature of the effect of an intercalating anticancer drug, i.e. doxorubicin, selected as a positive reference compound in our study, suggesting a fully distinct set of cellular perturbations. The current study thus illustrates that Fourier Transform Infrared (FTIR) analyses can be used to identify, among the perturbations induced on a given cancer cell line, the features common to a group of anticancer compounds as well as features specific to every single drug.
在本研究中,我们发现暴露于抗癌药物的人PC-3前列腺癌细胞的红外(IR)光谱能提供一个独特的机会,来获取细胞中所有主要生化成分(DNA、RNA、蛋白质、脂质等)的指纹图谱,并以高灵敏度识别抗癌药物诱导的代谢变化特征。我们在此研究了4种结构相关的强心甾类化合物(CS),即哇巴因、19-羟基-2″-氧代沃鲁查林、嚏根草毒素和19-羟基-嚏根草毒素对PC-3癌细胞的作用在无(对照)或有CS的情况下培养0至36小时的傅里叶变换红外(FTIR)相关特征。对于每个分子,单一光谱特征描述了大部分随时间变化的修饰,可能还有一个非常小的次要成分。表征四种CS各自作用的光谱特征是独特的,但与我们研究中选为阳性参考化合物的嵌入型抗癌药物阿霉素作用的特征相比非常相似,这表明存在一组完全不同的细胞扰动。因此,当前研究表明,傅里叶变换红外(FTIR)分析可用于在给定癌细胞系上诱导的扰动中,识别一组抗癌化合物共有的特征以及每种单一药物特有的特征。