Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/13055
Title: Modulation of telomerase and signal transduction proteins by Hexyl-ALA-Photodynamic Therapy (PDT) in human doxorubicin resistant cancer cell models
Authors: Chu, ESM
Yow, CMN
Keywords: Drug resistance
Hexyl-ALA
MAPK
Photodynamic therapy
Telomerase
Uterine sarcoma
Issue Date: 2012
Publisher: Elsevier Science Bv
Source: Photodiagnosis and photodynamic therapy, 2012, v. 9, no. 3, p. 243-255 How to cite?
Journal: Photodiagnosis and Photodynamic Therapy 
Abstract: Aims: This study employed a doxorubicin resistant (MES-SA-Dx5) human uterine sarcoma cell line and its counterpart (MES-SA), to elucidate the efficacy of aminolevulinic acid-hexylester (hexyl-ALA) mediated PDT at molecular and transcriptional levels. Methods: Hexyl-ALA generated protoporphyrin IX in both cells were determined by molecular probes using Confocal Laser Scanning Microscopy. The hexyl-ALA-PDT induced signal transduction proteins and mode of cell death were quantitated by CASE™ ELISA assays and DAPI staining. The modulation of hTERT mRNA expression and telomerase activity were investigated by TaqMan real-time PCR and ELISA respectively. Hexyl-ALA-PDT mediated cell migratory effect was determined by wound-healing assay. Results: The results demonstrated that mitochondria were the major target of hexyl-ALA. At LD30, hexyl-ALA-PDT significantly provoked an up-regulation of phosphorylated p38MAPK and JNK proteins in both cells. Hexyl-ALA-PDT down-regulated hTERT (a catalytic subunit of telomerase) mRNA expression and showed a strong correlation with diminished telomerase activity in both cells (MES-SA: r2=0.9932; MES-SA-Dx5: r2=0.9775). The suppression of cell migratory effect in both cells was obtained after hexyl-ALA-PDT. Further, 50% and 30% of apoptotic cells were attained at LD50, for wild-type and drug resistant cells respectively. Unlike the wild-type, a higher PDT dose was crucial to induce apoptosis in the drug resistant cells. Conclusions: Our study provides the first evidence that p38MAPK and JNK kinases played a vital role in triggering hexyl-ALA-PDT-induced apoptosis, down-regulated hTERT mRNA expression and telomerase activity in both proposed cells.In vivo studies are worth examining for the benefit of clinical applications in drug resistant cancers and PDT development.
URI: http://hdl.handle.net/10397/13055
DOI: 10.1016/j.pdpdt.2011.12.005
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