Undifferentiated Neuroblastoma Cells Are More Sensitive to Photogenerated Oxidative Stress Than Differentiated Cells.
Neuroblastoma is one of the most aggressive cancers and has a complex form of differentiation. We hypothesized that advanced cellular differentiation may alter the susceptibility of neuroblastoma to photodynamic treatment (PDT) and confer selective survival advantage. We demonstrated that hematoporphyrin uptake by undifferentiated SH-SY5Y cells was lower than that of differentiated counterparts, yet the former were more susceptible to PDT-induced oxidative stress killing. Photogenerated reactive oxygen species (ROS) in undifferentiated cells efficiently stimulated cell cycle arrest at G2/M phase, mitochondrial apoptotic pathway activation, the sustained phosphorylation of Akt/GSK-3β and ERK. Differentiated cells with more resistance to PDT exhibited a ROS-independent and a prolonged activation of ERK. Both SH-SY5Y cells exposed to PDT exhibited ROS-independent p38 and JNK activation. These results may have important implications for neuroblastoma patients undergoing photodynamic therapy.
Department of Medical Laboratory Science and Biotechnology, Fooyin University, Kaohsiung, Taiwan.
Chu-I
CI
Lee
Department of Chemistry, National Kaohsiung Normal University, Kaohsiung, Taiwan.
Jing-Huei
JH
Perng
Department of Medical Laboratory Science and Biotechnology, Fooyin University, Kaohsiung, Taiwan.|Department of Biological Science, National Sun Yat-sen University, Kaohsiung, Taiwan.
Huang-Yo
HY
Chen
Faculty of Medicine, Department of Biochemistry, Kaohsiung Medical University, Kaohsiung, Taiwan.
Yi-Ren
YR
Hong
Department of Nutrition and Health Science, Fooyin University, Kaohsiung, Taiwan.
Jyh-Jye
JJ
Wang
D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006415:Hematoporphyrins / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009447:Neuroblastoma / Q000188:drug therapy / Q000473:pathology*; D018384:Oxidative Stress / Q000187:drug effects*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism
D006415:Hematoporphyrins; D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species
APOPTOSIS; Akt/GSK-3β; DIFFERENTIATION; MAPKs; NEUROBLASTOMA; PHOTODYNAMIC THERAPY; REACTIVE OXYGEN SPECIES