1. Increased ceramide accumulation correlates with downregulation of the autophagy protein ATG-7 in MCF-7 cells sensitized to photodamage
- Author
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Separovic, Duska, Kelekar, Ameeta, Nayak, Arun K., Tarca, Adi L., Hanada, Kentaro, Pierce, Jason S., and Bielawski, Jacek
- Subjects
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CERAMIDES , *STATISTICAL correlation , *AUTOPHAGY , *PROTEINS , *CELL death , *CANCER cells , *BREAST cancer - Abstract
Abstract: The purpose of this study was to determine the sphingolipid (SL) profile in cells defective in autophagy protein ATG-7 and overall cell death after photodynamic therapy (PDT) with the photosensitizer Pc 4. MCF-7 human breast cancer cells with downregulated ATG-7 and their scrambled controls (Scr) were used. Exposure of ATG-7 knockdown cells to PDT led to increased cell killing. PDT evoked an early (2h) greater global increase in ceramides in ATG-7 defective cells compared to Scr cells. The total increases in dihydroceramide (DHceramide) were significant at 2 and 24h in both cell types post-PDT. The levels of sphingosine-1-phosphate (S1P) and sphingosine were decreased below resting levels at both time points irrespective of the cell type. The data imply that ceramide might be a marker of ATG-7 deficiency in cells sensitized to PDT. [Copyright &y& Elsevier]
- Published
- 2010
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