Increased ceramide accumulation correlates with downregulation of the autophagy protein ATG-7 in MCF-7 cells sensitized to photodamage

Duska Separovic, Ameeta Kelekar, Arun K. Nayak, Adi L. Tarca, Kentaro Hanada, Jason S. Pierce, Jacek Bielawski

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

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 (2 h) 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 24 h 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.

Original languageEnglish (US)
Pages (from-to)101-105
Number of pages5
JournalArchives of Biochemistry and Biophysics
Volume494
Issue number1
DOIs
StatePublished - Feb 1 2010

Keywords

  • Autophagy
  • Ceramide
  • Dihydroceramide
  • Photodynamic therapy

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