Rello-Varona Santiago, Stockert Juan Carlos, Cañete Magdalena, Acedo Pilar, Villanueva Angeles
Departamento de Biología, Facultad de Ciencias, Universidad Autónoma de Madrid, C/ Darwin 2, E-28049 Madrid, Spain.
Int J Oncol. 2008 Jun;32(6):1189-96. doi: 10.3892/ijo_32_6_1189.
Photodynamic therapy (PDT) is a tool against neoplastic and non-neoplastic diseases. PDT is capable to induce different cell death mechanisms in vitro, triggered in a dose-dependent manner. Relationships between PDT and apoptosis or necrosis induction are well-known, but other cell death mechanisms triggered after PDT are less understood. Here we present our results in p53-deficient human cervix carcinoma HeLa cells subjected to sublethal PDT treatments (mortality about 40%) using Zn(II)-phthalocyanine (ZnPc) incorporated into liposomes. We obtained a rapid metaphase blockage of cells that also showed clearly altered configurations of the mitotic spindle. Cell cycle arrest was followed by aneuploidisation and cell death with apoptotic morphology. Apoptosis was also confirmed by occurrence of PARP cleavage and Bax translocation to mitochondria. These features are components of the cell death mechanism known as mitotic catastrophe and represent, to our knowledge, the first description of this cell death modality after PDT with ZnPc.
光动力疗法（PDT）是一种治疗肿瘤性和非肿瘤性疾病的手段。PDT能够在体外诱导不同的细胞死亡机制，且呈剂量依赖性触发。PDT与凋亡或坏死诱导之间的关系已为人熟知，但PDT触发的其他细胞死亡机制却鲜为人知。在此，我们展示了使用包裹于脂质体中的锌（II）-酞菁（ZnPc）对p53基因缺陷的人宫颈癌HeLa细胞进行亚致死性PDT处理（死亡率约40%）后的结果。我们观察到细胞迅速出现中期阻滞，同时有丝分裂纺锤体的形态也明显改变。细胞周期阻滞之后出现非整倍体化以及具有凋亡形态的细胞死亡。PARP裂解以及Bax转位至线粒体的现象也证实了细胞凋亡的发生。这些特征是被称为有丝分裂灾难的细胞死亡机制的组成部分，据我们所知，这是首次对ZnPc介导的PDT后这种细胞死亡方式的描述。
