NDLI: Antitumor Effects of Photodynamic Therapy Are Potentiated by 2-Methoxyestradiol A SUPEROXIDE DISMUTASE INHIBITOR

Content Provider	Journal of Biological Chemistry (JBC)
Author	Ğb, Jakub Goł Nowis, Dominika Skrzycki, Michał Czeczot, Hanna Barańczyk-Kuźma, Anna Wilczyński, Grzegorz M. Makowski, Marcin Mróz, Paweł Kozar, Katarzyna Kamiński, Rafał Jalili, Ahmad Kopeć, Maciej Grzela, Tomasz Jakóbisiak, Marek
Abstract	Photodynamic therapy (PDT), a promising therapeutic modality for the management of solid tumors, is a two-phase treatment consisting of a photosensitizer and visible light. Increasing evidence indicates that tumor cells in regions exposed to sublethal doses of PDT can respond by rescue responses that lead to insufficient cell death. We decided to examine the role of superoxide dismutases (SODs) in the effectiveness of PDT and to investigate whether 2-methoxyestradiol (2-MeOE2), an inhibitor of SODs, is capable of potentiating the antitumor effects of this treatment regimen. In the initial experiment we observed that PDT induced the expression of MnSOD but not Cu,Zn-SOD in cancer cells. Pretreatment of cancer cells with a cell-permeable SOD mimetic, Mn(II)-tetrakis(4-benzoic acid)porphyrin chloride, and transient transfection with the MnSOD gene resulted in a decreased effectiveness of PDT. Inhibition of SOD activity in tumor cells by preincubation with 2-MeOE2 produced synergistic antitumor effects when combined with PDT in 3 murine and 5 human tumor cell lines. The combination treatment was also effective in vivo producing retardation of the tumor growth and prolongation of the survival of tumor-bearing mice. We conclude that inhibition of MnSOD activity by 2-MeOE2 is an effective treatment modality capable of potentiating the antitumor effectiveness of PDT.
Related Links	http://www.jbc.org/content/278/1/407.abstract
Ending Page	414
Starting Page	407
Page Count	8
File Format	HTM / HTML PDF
ISSN	00219258
Journal	Journal of Biological Chemistry (JBC)
Issue Number	1
Volume Number	278
DOI	10.1074/jbc.M209125200
e-ISSN	1083351X
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2003-01-03
Access Restriction	Open
Subject Keyword	Photodynamic therapy (PDT) Mn(II)-tetrakis(4-benzoic acid)porphyrin chloride (MnTBAP) Lewis lung carcinoma (LLC) Superoxide dismutase (SOD) Phosphate-buffered saline (PBS) MOLECULAR BASIS OF CELL AND DEVELOPMENTAL BIOLOGY
Alternative Title	Antitumor Effects of Photodynamic Therapy Are Potentiated by 2-Methoxyestradiol
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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