Undifferentiated Neuroblastoma Cells Are More Sensitive to Photogenerated Oxidative Stress Than Differentiated Cells

• Published in: Journal of cellular biochemistry Vol. 116; no. 9; pp. 2074 - 2085
• Main Authors: Lee, Chu-I, Perng, Jing-Huei, Chen, Huang-Yo, Hong, Yi-Ren, Wang, Jyh-Jye
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.09.2015; Wiley Subscription Services, Inc
• Subjects: Akt/GSK-3β; APOPTOSIS; Cell Differentiation - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; DIFFERENTIATION; Hematoporphyrins - pharmacokinetics; Hematoporphyrins - pharmacology; Humans; MAP Kinase Signaling System - drug effects; MAPKs; NEUROBLASTOMA; Neuroblastoma - drug therapy; Neuroblastoma - pathology; Oxidative Stress - drug effects; Photochemotherapy; PHOTODYNAMIC THERAPY; Photosensitizing Agents - pharmacokinetics; Photosensitizing Agents - pharmacology; REACTIVE OXYGEN SPECIES; Reactive Oxygen Species - metabolism; APOPTOSIS; PHOTODYNAMIC THERAPY; REACTIVE OXYGEN SPECIES; NEUROBLASTOMA; Akt/GSK-3β; DIFFERENTIATION; MAPKs
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.25165

ABSTRACT 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. J. Cell. Biochem. 116: 2074–2085, 2015. © 2015 Wiley Periodicals, Inc.