Antitumor Effects of Photodynamic Therapy Are Potentiated by 2-Methoxyestradiol

Ğb, Jakub Goł; Nowis, Dominika; Skrzycki, Michał; Hanna, Calvin; Barańczyk‐Kuźma, Anna; Wilczyński, Grzegorz M.; Makowski, Marcin; Mróz, Paweł; Kozar, Katarzyna; Kaminski, Rafal; Jalili, Ahmad; Kopec, Maciej; Grzela, Tomasz; Jakóbisiak, Marek

doi:10.1074/jbc.m209125200

Cited by 114 publications

(40 citation statements)

References 39 publications

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“…Treating mESCs with increasing concentration of MnSOD specific inhibitor, 2-Methoxyoestradiol (2-MeOE2)26 showed decreased SOD activity (Supplementary Fig. 5a).…”

Section: Resultsmentioning

confidence: 99%

Novel Role of Mitochondrial Manganese Superoxide Dismutase in STAT3 Dependent Pluripotency of Mouse Embryonic Stem Cells

Sheshadri

Jahnavi

et al. 2015

Sci Rep

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Leukemia Inhibitory Factor (LIF)/Signal transducer and activator of transcription 3 (STAT3) signaling pathway maintains the stemness and pluripotency of mouse embryonic stem cells (mESCs). Detailed knowledge on key intermediates in this pathway as well as any parallel pathways is largely missing. We initiated our study by investigating the effect of small molecule Curcumin on various signalling pathways essential for self-renewal. Curcumin sustained the LIF independent self-renewal of mESCs and induced pluripotent stem cells (miPSCs) in a STAT3 activity dependent manner. Gene expression analysis showed LIF/STAT3 and redox signaling components to be majorly modulated. Amongst ROS genes, expression of Manganese Superoxide Dismutase (MnSOD) specifically relied on STAT3 signaling as evidenced by STAT3 inhibition and reporter assay. The silencing of MnSOD, but not Cu-ZnSOD expression, resulted in the loss of mESC pluripotency in presence of LIF, and the overexpression of MnSOD is sufficient for maintaining the expression of pluripotent genes in the absence of STAT3 signaling. Finally, we demonstrate MnSOD to stabilize the turnover of pluripotent proteins at the post-translational level by modulating proteasomal activity. In conclusion, our findings unravel a novel role of STAT3 mediated MnSOD in the self-renewal of mESCs.

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“…Treating mESCs with increasing concentration of MnSOD specific inhibitor, 2-Methoxyoestradiol (2-MeOE2)26 showed decreased SOD activity (Supplementary Fig. 5a).…”

Section: Resultsmentioning

confidence: 99%

Novel Role of Mitochondrial Manganese Superoxide Dismutase in STAT3 Dependent Pluripotency of Mouse Embryonic Stem Cells

Sheshadri

Jahnavi

et al. 2015

Sci Rep

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“…For example, superoxide dismutase (SOD) over-expression or treatment with SOD mimetics have been shown to counteract the cytotoxic effect of PDT. 41 An increase of the SOD activity has been also observed in various cancer cell types following PDT, and this is associated with a decrease in glutathione peroxidase and catalase activities. 42 The third cytoprotective mechanism involves proteins whose encoding genes are themselves induced by PDT.…”

Section: Basic Components Of Photodynamic Therapymentioning

confidence: 99%

Photodynamic therapy of cancer: An update

Agostinis

Berg

Cengel

et al. 2011

CA: A Cancer Journal for Clinicians

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Photodynamic therapy (PDT) is a clinically approved, minimally invasive therapeutic procedure that can exert a selective cytotoxic activity toward malignant cells. The procedure involves administration of a photosensitizing agent followed by irradiation at a wavelength corresponding to an absorbance band of the sensitizer. In the presence of oxygen, a series of events lead to direct tumor cell death, damage to the microvasculature and induction of a local inflammatory reaction. Clinical studies revealed that PDT can be curative particularly in early-stage tumors. It can prolong survival in inoperable cancers and significantly improve quality of life. Minimal normal tissue toxicity, negligible systemic effects, greatly reduced long-term morbidity, lack of intrinsic or acquired resistance mechanisms, and excellent cosmetic as well as organ function-sparing effects of this treatment make it a valuable therapeutic option for combination treatments. With a number of recent technological improvements, PDT has the potential to become integrated into the mainstream of cancer treatment.

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“…Singlet oxygen and superoxide anion have been demonstrated to play a main role in the cytotoxic effects induced by PDT [164,165]. SOD1 and SOD2 scavenged cells from singlet oxygen and significant extent the antitumor efficacy of PDT [156,166,167]. Combinations of SOD inhibitor with PDT might result in significant increase in the efficiency of anticancer treatment [154].…”

Section: Enzymatic Antioxidantsmentioning

confidence: 99%

“…2-methoxyestradiol (2-MeOE2) was shown to selectively inhibit the activity of superoxide dismutases [170]. PDT with 2-MeOE2 selectively enhance free radical generation and suppress antioxidant defenses, which significantly increases the effectiveness of therapy [156].…”

Section: Enzymatic Antioxidantsmentioning

confidence: 99%

“…Photodynamic therapy (PDT), a promising therapy for solid tumors, based on the photochemical reaction produces singlet oxygen and other forms of reactive oxygen, such as superoxide ion, hydrogen peroxide, hydroxyl radical [156][157][158][159][160]. Tumor cells can respond to photodynamic damage by apoptosis or necrosis [161][162][163].…”

Section: Enzymatic Antioxidantsmentioning

confidence: 99%

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