Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital and Medical Faculty, University of Oslo, Oslo, Norway.
Cancer Lett. 2013 Oct 1;339(1):25-32. doi: 10.1016/j.canlet.2013.07.026. Epub 2013 Jul 31.
Photodynamic therapy (PDT) with a light-activated drug is an approved modality for cancer treatment. Hexaminolevulinate (HAL), a hexylester of 5-aminolevulinic acid as the photosensitising protoporphyrin IX (PpIX) precursor, is clinically used for both PDT and photodetection. Our previous studies have shown that HAL-PDT can effectively induce apoptosis in several human blood malignant cell lines. However, the mechanisms involved in the apoptotic induction are still not fully elucidated. In this study we have focused on the role of cellular lamin A/C in the apoptotic induction. HAL-PDT-mediated apoptosis was confirmed by various techniques including fluorescence microscopy and electron microscopy in both human B-cell lymphoma Ramos and Daudi cell lines. The lamin A/C, together with caspases-6 and -3, was cleaved during the apoptosis. Western blots, immunocytochemistry, fluorescence microscopy and electron microscopy demonstrated that the specific caspase-6 inhibitor abrogated the HAL-PDT-mediated cleavages of both caspase-6 and lamin A/C and subsequent apoptosis in these two cell lines, suggesting that the cleavage of lamin A/C by the caspase-6 activation is crucial for such apoptotic induction.
光动力学疗法（PDT）使用光激活药物是一种已被批准的癌症治疗方法。六氨基乙酰丙酸（HAL）是 5-氨基乙酰丙酸的己基酯，是光敏原卟啉 IX（PpIX）的前体，临床上用于 PDT 和光检测。我们之前的研究表明，HAL-PDT 可以有效诱导几种人血液恶性细胞系发生细胞凋亡。然而，涉及细胞凋亡诱导的机制尚未完全阐明。在这项研究中，我们专注于细胞层粘连蛋白 A/C 在细胞凋亡诱导中的作用。通过荧光显微镜和电子显微镜等各种技术证实了 HAL-PDT 介导的细胞凋亡，在人 B 细胞淋巴瘤 Ramos 和 Daudi 细胞系中均观察到这一现象。层粘连蛋白 A/C 与 caspase-6 和 caspase-3 一起在凋亡过程中被切割。Western blot、免疫细胞化学、荧光显微镜和电子显微镜表明，特异性 caspase-6 抑制剂阻断了这两种细胞系中 caspase-6 和层粘连蛋白 A/C 的 HAL-PDT 介导的切割以及随后的细胞凋亡，这表明 caspase-6 激活导致的层粘连蛋白 A/C 的切割对于这种细胞凋亡诱导至关重要。
