Increased ceramide accumulation correlates with downregulation of the autophagy protein ATG-7 in MCF-7 cells sensitized to photodamage.
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.
Separovic
Duska
D
Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48201, USA. dseparovic@wayne.edu
Kelekar
Ameeta
A
Nayak
Arun K
AK
Tarca
Adi L
AL
Hanada
Kentaro
K
Pierce
Jason S
JS
Bielawski
Jacek
J
D001343:Autophagy; D000071193:Autophagy-Related Protein 7; D045744:Cell Line, Tumor; D002518:Ceramides / Q000378:metabolism*; D015536:Down-Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D044764:Ubiquitin-Activating Enzymes / Q000235:genetics / Q000378:metabolism*
D002518:Ceramides; D017319:Photosensitizing Agents; C509349:ATG7 protein, human; D000071193:Autophagy-Related Protein 7; D044764:Ubiquitin-Activating Enzymes