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

共 25 条

[11] The use of PVP as a polymeric carrier to improve the plasma half-life of drugs [J].

Kaneda, Y ;

Tsutsumi, Y ;

Yoshioka, Y ;

Kamada, H ;

Yamamoto, Y ;

Kodaira, H ;

Tsunoda, S ;

Okamoto, T ;

Mukai, Y ;

Shibata, H ;

Nakagawa, S ;

Mayumi, T .

BIOMATERIALS, 2004, 25 (16) :3259-3266

[12] Delayed oxidative photodamage induced by photodynamic therapy [J].

Kessel, D ;

Luo, Y .

PHOTOCHEMISTRY AND PHOTOBIOLOGY, 1996, 64 (03) :601-604

[13] Mitochondrial photodamage and PDT-induced apoptosis [J].

Kessel, D ;

Luo, Y .

JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY, 1998, 42 (02) :89-95

[14] Free radical production in hypoxic pulmonary artery smooth muscle cells [J].

Killilea, DW ;

Hester, R ;

Balczon, R ;

Babal, P ;

Gillespie, MN .

AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 2000, 279 (02) :L408-L412

[15] EXPERIMENTAL GROUNDS FOR USING CHLORIN E(6) IN THE PHOTODYNAMIC THERAPY OF MALIGNANT-TUMORS [J].

KOSTENICH, GA ;

ZHURAVKIN, IN ;

ZHAVRID, EA .

JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY, 1994, 22 (03) :211-217

[16] EVALUATION OF THE PROBE 2',7'-DICHLOROFLUORESCIN AS AN INDICATOR OF REACTIVE OXYGEN SPECIES FORMATION AND OXIDATIVE STRESS [J].

LEBEL, CP ;

ISCHIROPOULOS, H ;

BONDY, SC .

CHEMICAL RESEARCH IN TOXICOLOGY, 1992, 5 (02) :227-231

[17] Spectral-luminescent studies of the photolon photosensitizer in model media and in blood of oncological patients [J].

Parkhots, M.V. ;

Knyukshto, V.N. ;

Isakov, G.A. ;

Petrov, P.T. ;

Lepeshkevich, S.V. ;

Khairullina, A.Ya. ;

Dzhagarov, B.A. .

Journal of Applied Spectroscopy, 2003, 70 (06) :921-926

[18]

Petrov P.T., 2004, ACTA BIOOPTIC INFORM, V10, P6

[19]

Ramaswamy B, 2005, INT J ONCOL, V26, P1501

[20] INVITRO PHOTOSENSITIZATION .1. CELLULAR UPTAKE AND SUBCELLULAR-LOCALIZATION OF MONO-L-ASPARTYL CHLORIN E6, CHLORO-ALUMINUM SULFONATED PHTHALOCYANINE, AND PHOTOFRIN-II [J].

ROBERTS, WG ;

BERNS, MW .

LASERS IN SURGERY AND MEDICINE, 1989, 9 (02) :90-101

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