xCT (SLC7A11) expression confers intrinsic resistance to physical plasma treatment in tumor cells

被引：52

作者：

Bekeschus, Sander ^{[1
]}

Eisenmann, Sebastian ^{[1
]}

Sagwal, Sanjeev Kumar ^{[1
]}

Bodnar, Yana ^{[1
]}

Moritz, Juliane ^{[1
]}

Poschkamp, Broder ^{[1
,2
]}

Stoffels, Ingo ^{[3
]}

Emmert, Steffen ^{[4
]}

Madesh, Muniswamy ^{[6
]}

Weltmann, Klaus-Dieter ^{[1
]}

von Woedtke, Thomas ^{[1
,5
]}

Gandhirajan, Rajesh Kumar ^{[1
]}

机构：

[1] Leibniz Inst Plasma Sci & Technol INP Greifswald, ZIK Plasmatis, Felix Hausdorff Str 2, D-17489 Greifswald, Germany

[2] Greifswald Univ, Med Ctr, Dept Gen Visceral Thorac & Vasc Surg, D-17475 Greifswald, Germany

[3] Univ Duisburg Essen, Univ Hosp Essen, Dept Dermatol Venereol & Allergol, D-45122 Essen, Germany

[4] Rostock Univ, Clin Dermatol & Venereol, Med Ctr, Walther Rathenau Str 48, D-17489 Rostock, Germany

[5] Inst Hyg & Environm Med, Walther Rathenau Str 48, D-17489 Greifswald, Germany

[6] Univ Texas Hlth San Antonio, Ctr Precis Med, Dept Med, San Antonio, TX USA

来源：

REDOX BIOLOGY | 2020年 / 30卷

关键词：

Cancer; Glutathione; kINPen; Melanoma; Plasma medicine; HYDROGEN-PEROXIDE; CANCER-CELLS; COLD-PLASMA; IN-VITRO; MITOCHONDRIAL; GLUTATHIONE; ANTIPORTER; EPIGENETICS; GROWTH; DEMETHYLATION;

D O I：

10.1016/j.redox.2019.101423

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：

Cold physical plasma is a partially ionized gas investigated as a new anticancer tool in selectively targeting cancer cells in monotherapy or in combination with therapeutic agents. Here, we investigated the intrinsic resistance mechanisms of tumor cells towards physical plasma treatment. When analyzing the dose-response relationship to cold plasma-derived oxidants in 11 human cancer cell lines, we identified four 'resistant' and seven 'sensitive' cell lines. We observed stable intracellular glutathione levels following plasma treatment only in the 'resistant' cell lines indicative of altered antioxidant mechanisms. Assessment of proteins involved in GSH metabolism revealed cystine-glutamate antiporter xCT (SLC7A11) to be significantly more abundant in the 'resistant' cell lines as compared to 'sensitive' cell lines. This decisive role of xCT was confirmed by pharmacological and genetic inhibition, followed by cold physical plasma treatment. Finally, microscopy analysis of ex vivo plasma-treated human melanoma punch biopsies suggested a correlation between apoptosis and basal xCT protein abundance. Taken together, our results demonstrate that xCT holds the potential as a biomarker predicting the sensitivity of tumor cells towards plasma treatment.

引用

页数：10

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