Neuroblastoma is one of the most aggressive cancers and has a complex form of differentiation. We hypothesized that the advanced cellular differentiation may alter the susceptibility of neuroblastoma to photodynamic therapy (PDT) and have a selective survival advantage. We compared the photocytotoxicity treated by Hematoporphyrin (Hp) for PDT on human neuroblastoma SH-SY5Y cells with retinoic acid (RA)-differentiated SH-SY5Y cells. The undifferentiated neuroblastoma cells were shown to cause elevated photocytotoxic effect by MTT assay and also confirmed by Annexin V-FITC/PI staining. In undifferentiated cells, Hp-PDT increased the generation of intracellular reactive oxygen species (ROS), the loss of mitochondrial membrane potential, characteristic chromatin condensation displaying, PARP cleavage, the downregulated expression of Bcl-2, and the activation of caspase-9, -3 was more significant than that of the differentiated cells. In undifferentiated SH-SY5Y cells, cell cycle arrest at G2/M phase was accompanied by the decrease in cyclin B1 level, and could be reversed by the disruption of intracellular ROS caused by PDT. Furthermore, the ROS scavenger markedly inhibited Hp-PDT induced activation of caspase-3, a sustained phosphorylation of Akt/GSK-3£] and ERK, and cytotoxicity in undifferentiated SH-SY5Y cells, but not in differentiated SH-SY5Y cells. Blockage of p38 and JNK activation can significantly attenuate PDT-induced viability loss in both SH-SY5Y cells, but the less significant activation of p38 and JNK, as well as more significant phosphorylation of Akt and GSK-3£], and a prolonged ERK activation appeared to make differentiated SH-SY5Y cells more resistant to photocytotoxicity. Collectively, these data suggested that differentiated SH-SY5Y cells were more resistant to PDT induced apoptosis than undifferentiated SH-SY5Y cells, and ROS played the most important regulatory role on the susceptibility to Hp-PDT between undifferentiated and differentiated neuroblastoma cells. These results may have important implications for neuroblastoma patients undergoing PDT.
| Identifer | oai:union.ndltd.org:NSYSU/oai:NSYSU:etd-0716112-123712 |
| Date | 16 July 2012 |
| Creators | Chen, Huang-Yo |
| Contributors | Jiin-Tsuey Cheng, Yi-Ren Hong, Chi-Huei Wang, Chu-I Lee |
| Publisher | NSYSU |
| Source Sets | NSYSU Electronic Thesis and Dissertation Archive |
| Language | Cholon |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0716112-123712 |
| Rights | user_define, Copyright information available at source archive |
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