Soriano Jorge, Villanueva Angeles, Stockert Juan Carlos, Cañete Magdalena
Department of Biology, University Autonomous of Madrid, 28049 Madrid, Spain.
Int J Mol Sci. 2014 Dec 9;15(12):22772-85. doi: 10.3390/ijms151222772.
Photodynamic therapy (PDT) is a cancer treatment modality based on the administration of a photosensitizer (PS), which accumulates preferentially in tumor cells. Subsequent irradiation of the neoplastic area triggers a cascade of photochemical reactions that leads to the formation of highly reactive oxygen species responsible for cell inactivation. Photodynamic treatments in vitro are performed with the PS, zinc-phthalocyanine (ZnPc). The PS is near the plasma membrane during uptake and internalization. Inactivation clearly occurs by a necrotic process, manifested by nuclear pyknosis, negative TUNEL and Annexin V assays and non-relocation of cytochrome c. In contrast, by increasing the incubation time, ZnPc is accumulated in the Golgi apparatus and produces cell inactivation with characteristics of apoptosis and necrosis: TUNEL positive, relocated cytochrome c and negative Annexin V assay. This type of death produces a still undescribed granulated nuclear morphology, which is different from that of necrosis or apoptosis. This morphology is inhibited by necrostatin-1, a specific inhibitor of regulated necrosis.
光动力疗法(PDT)是一种基于施用光敏剂(PS)的癌症治疗方式,光敏剂优先在肿瘤细胞中蓄积。随后对肿瘤区域进行照射会引发一系列光化学反应,导致形成高活性氧物质,从而使细胞失活。体外光动力治疗使用的光敏剂是锌酞菁(ZnPc)。在摄取和内化过程中,光敏剂靠近质膜。失活显然是通过坏死过程发生的,表现为核固缩、TUNEL检测阴性、膜联蛋白V检测阴性以及细胞色素c未重新定位。相比之下,通过延长孵育时间,ZnPc会在高尔基体中蓄积,并产生具有凋亡和坏死特征的细胞失活:TUNEL检测阳性、细胞色素c重新定位以及膜联蛋白V检测阴性。这种类型的死亡会产生一种尚未描述的颗粒状核形态,与坏死或凋亡的核形态不同。这种形态受到坏死抑制因子-1(一种调节性坏死的特异性抑制剂)的抑制。