Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/9064
Title: Photodynamic therapy (PDT) - Initiation of apoptosis via activation of stress-activated p38 MAPK and JNK signal pathway in H460 cell lines
Authors: Wu, RWK
Yow, CMN
Wong, CK
Lam, YH
Keywords: 5-Aminolevulinic acid
Apoptosis
Bcl-2
Lung carcinoma
Photodynamic therapy
Protoporphyrin IX
Issue Date: 2011
Publisher: Elsevier Science Bv
Source: Photodiagnosis and photodynamic therapy, 2011, v. 8, no. 3, p. 254-263 How to cite?
Journal: Photodiagnosis and Photodynamic Therapy 
Abstract: Aims: The purpose of this study was to investigate the photoefficacies of protoporphyrin IX (PpIX) generated by drug precursor 5-aminolevulinic acid (ALA) and its hexyl ester (H-ALA) on two human non-small lung carcinoma cell lines (H460/Bcl-2 and H460/neo). Main methods: Drug uptake and the photoefficacies of PpIX were measured by flow cytometry and MTT assay; while the mode of cell death and alternation of signal transduction pathways were studied with 4',6-diamidino-2-phenylindole (DAPI) staining and Western blot analysis, respectively. Key findings: The flow cytometric analysis of H-ALA (5μM) uptake revealed optimal fluorescent intensity at 8h incubation, while ALA (0.5mM) was still far from saturation. The LD 30 of H-ALA-PDT was 30μM, 2J/cm 2, while the LD 30 of ALA-PDT was 3mM, 2J/cm 2. The dark toxicities mediated by both pro-drug H-ALA and ALA were negligible. By DAPI staining, apoptotic cell death was observed. In addition, by Western blot analysis, H-ALA- and ALA-mediated PDT initiated apoptotic cell death via the up-regulation and activation of p38 mitogen activated protein kinase (MAPK), the stress-activated c-jun N-terminal kinases (JNK) and ERK. Significance: These results suggested that H-ALA and ALA mediated PDT displayed similar photocytotoxicities towards the two non-small lung cancer cells. Our present study also demonstrates H-ALA or ALA mediated PDT in H460 cells are closely related to the activation of p38 MAPK and JNK signalling pathway.
URI: http://hdl.handle.net/10397/9064
DOI: 10.1016/j.pdpdt.2010.12.002
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