TY - JOUR
T1 - Apoptosis and expression of cytokines triggered by pyropheophorbide-a methyl ester-mediated photodynamic therapy in nasopharyngeal carcinoma cells
AU - Li, K. M.
AU - Sun, X.
AU - Koon, H. K.
AU - Leung, W. N.
AU - Fung, M. C.
AU - WONG, Ricky N S
AU - Lung, Maria L.
AU - Chang, C. K.
AU - MAK, Nai Ki
N1 - Funding Information:
This work was supported by the Research Grant Council of Hong Kong (HKUST/CA03-04/2 and HKBU2052/02M) and HKBU (FRG/03-04/II-08).
PY - 2006/12
Y1 - 2006/12
N2 - The photodynamic properties of pyropheophorbide-a methyl ester (MPPa), a semi-synthetic photosensitizer derived from chlorophyll a, were evaluated in a human nasopharyngeal carcinoma HONE-1 cell line. MPPa was non-toxic to the HONE-1. At the concentrations of 0.5-2 μM, MPPa-mediated a drug dose-dependent photocytotoxicity in the HONE-1 cells. Confocal microscopy revealed a subcellular localization of MPPa in mitochondria and the Golgi apparatus. MPPa PDT-induced apoptosis was associated with the collapse of mitochondrial membrane potential, release of cytochrome c, the up-regulation of endoplasmic reticulum (ER) stress proteins (calnexin, Grp 94 and Grp78), and the activation of caspases-3 and -9. The photocytotoxicity was reduced by the corresponding specific caspase inhibitors. MPPa PDT-treated HONE-1 cells also up-regulated the gene expression of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and beta-chemokines (MIP-1β, MPIF-1, and MPIF-2). These results suggest that the MPPa may be developed as a chlorophyll-based photosensitizer for the treatment of nasopharyngeal carcinoma.
AB - The photodynamic properties of pyropheophorbide-a methyl ester (MPPa), a semi-synthetic photosensitizer derived from chlorophyll a, were evaluated in a human nasopharyngeal carcinoma HONE-1 cell line. MPPa was non-toxic to the HONE-1. At the concentrations of 0.5-2 μM, MPPa-mediated a drug dose-dependent photocytotoxicity in the HONE-1 cells. Confocal microscopy revealed a subcellular localization of MPPa in mitochondria and the Golgi apparatus. MPPa PDT-induced apoptosis was associated with the collapse of mitochondrial membrane potential, release of cytochrome c, the up-regulation of endoplasmic reticulum (ER) stress proteins (calnexin, Grp 94 and Grp78), and the activation of caspases-3 and -9. The photocytotoxicity was reduced by the corresponding specific caspase inhibitors. MPPa PDT-treated HONE-1 cells also up-regulated the gene expression of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and beta-chemokines (MIP-1β, MPIF-1, and MPIF-2). These results suggest that the MPPa may be developed as a chlorophyll-based photosensitizer for the treatment of nasopharyngeal carcinoma.
KW - Apoptosis
KW - Mitochondrial membrane potential
KW - Nasopharyngeal carcinoma
KW - Photodynamic therapy
KW - Pyropheophorbide-a methyl ester
UR - http://www.scopus.com/inward/record.url?scp=33845981082&partnerID=8YFLogxK
U2 - 10.1016/j.pdpdt.2006.09.001
DO - 10.1016/j.pdpdt.2006.09.001
M3 - Article
AN - SCOPUS:33845981082
SN - 1572-1000
VL - 3
SP - 247
EP - 258
JO - Photodiagnosis and Photodynamic Therapy
JF - Photodiagnosis and Photodynamic Therapy
IS - 4
ER -