Photolon™, a chlorin e6 derivative, triggers ROS production and light-dependent cell death via necrosis

被引：42

作者：

Copley, Louise ^{[1
]}

van der Watt, Pauline ^{[1
]}

Wirtz, Karel W. ^{[2
]}

Parker, M. Iqbal ^{[1
]}

Leaner, Vima D. ^{[1
]}

机构：

[1] Univ Cape Town, Fac Hlth Sci, Div Med Biochem, ZA-7925 Cape Town, South Africa

[2] Univ Utrecht, CBLE, Dept Biochem Lipids, NL-3508 TC Utrecht, Netherlands

来源：

INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY | 2008年 / 40卷 / 02期

基金：

英国医学研究理事会;

关键词：

photodynamic therapy; Photolon (TM) (fotolon); cancer; ROS production; necrosis;

D O I：

10.1016/j.biocel.2007.07.014

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Photolon (TM) is a photosensitiser with demonstrated potential as an anti-tumour agent. In this study, an in vitro investigation was performed to determine the mechanism of Photolon (TM) -induced cell death. Cell killing was observed in a light-dependent manner and light-activated Photolon (TM) resulted in a significant production of reactive oxygen species (ROS), which could be blocked by type I ROS scavengers. Inhibition of ROS production using Trolox prevented Photolon (TM) -induced cell death. Light-activated Photolon (TM) caused no increase in caspase-3/7 activity, but a rapid increase in lactate dehydrogenase (LDH) release suggesting a loss of membrane integrity and subsequent cell death by necrosis. We conclude that the mechanism of Photolon (TM)- induced cell death involves the induction of ROS via a type I mechanism, which is ultimately responsible for cell killing by necrosis. (c) 2007 Elsevier Ltd. All rights reserved.

引用

页码：227 / 235

页数：9

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