Cañete M, Ortiz A, Juarranz A, Villanueva A, Nonell S, Borrell J I, Teixidó J, Stockert J C
Departamento de Biología, Facultad de Ciencias, Universidad Autónoma de Madrid, Canto Blanco, Spain.
Anticancer Drug Des. 2000 Apr;15(2):143-50.
In this study we describe photokilling properties and effects on the mitotic index (MI) of cultured HeLa cells induced by palladium(II)-tetraphenylporphycene (PdTPP(0)). The drug was synthesized by refluxing tetraphenylporphycene (TPP(0)) and PdCl2 in dimethylformamide, followed by evaporation and purification by chromatography. Cells were treated with different concentrations of PdTPPo incorporated into dipalmitoylphosphatidylcholine liposomes, and red light irradiation (lambda > 600 nm) was performed at 21 mW/cm2. No dark toxicity was found when the drug was applied under our experimental conditions. Using lethal (LD(100)) treatments, cells showed the immediate occurrence of bubbles on the plasma membrane, whereas homogeneous nuclear condensation and loss of cytoplasm appeared 3-24 h later. An increased MI was found 6-8 h after sublethal LD(25) and LD(40) treatments as well as a high proportion of abnormal metaphases with altered spindle microtubules. Chromatin condensation and fragmentation were observed 8 h after LD(75) treatments. These results show that in comparison with TPP(0), the new sensitizer PdTPPo has more efficient photokilling properties which could be very valuable for the photodynamic therapy of cancer.
在本研究中,我们描述了钯(II)-四苯基卟啉(PdTPP(0))对培养的HeLa细胞的光杀伤特性及其对有丝分裂指数(MI)的影响。该药物通过在二甲基甲酰胺中回流四苯基卟啉(TPP(0))和PdCl2合成,然后蒸发并通过色谱法纯化。用掺入二棕榈酰磷脂酰胆碱脂质体的不同浓度的PdTPPo处理细胞,并在21 mW/cm2下进行红光照射(λ> 600 nm)。在我们的实验条件下应用该药物时未发现暗毒性。使用致死(LD(100))处理时,细胞在质膜上立即出现气泡,而均匀的核浓缩和细胞质丧失在3 - 24小时后出现。在亚致死的LD(25)和LD(40)处理6 - 8小时后发现有丝分裂指数增加,以及高比例的具有改变的纺锤体微管的异常中期。在LD(75)处理8小时后观察到染色质浓缩和碎片化。这些结果表明,与TPP(0)相比,新型敏化剂PdTPPo具有更有效的光杀伤特性,这对于癌症的光动力治疗可能非常有价值。