Antitumor effects of photodynamic therapy are potentiated by 2-methoxyestradiol: A superoxide dismutase inhibitor

Jakub Gołab, Dominika Nowis, Michal Skrzycki, Hanna Czeczot, Anna Barańczyk-Kuźma, Grzegorz M. Wilczyński, Marcin Makowski, Pawel Mróz, Katarzyna Kozar, Rafał Kamiński, Ahmad Jalili, Maciej Kopeć, Tomasz Grzela, Marek Jakóbisiak

Research output: Contribution to journalArticlepeer-review

99 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)407-414
Number of pages8
JournalJournal of Biological Chemistry
Volume278
Issue number1
DOIs
StatePublished - Jan 3 2003

Fingerprint Dive into the research topics of 'Antitumor effects of photodynamic therapy are potentiated by 2-methoxyestradiol: A superoxide dismutase inhibitor'. Together they form a unique fingerprint.

Cite this