Journal
CANCER INVESTIGATION
Volume 30, Issue 1, Pages 27-37Publisher
TAYLOR & FRANCIS INC
DOI: 10.3109/07357907.2011.629379
Keywords
Autophagy; Ceramide; Glioblastoma; Glucosylceramide synthase; Temozolomide
Categories
Funding
- Ministry of University and Scientific and Technological Research PRIN
- FIRST
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Glioblastoma is a deadly cancer with intrinsic chemoresistance. Understanding this property will aid in therapy. Glucosylceramide synthase (GCS) is associated with resistance and poor outcome; little is known about glioblastomas. In glioblastoma cells, temozolomide and paclitaxel induce ceramide increase, which in turn promotes cytotoxicity. In drug-resistant cells, both drugs are unable to accumulate ceramide, increased expression and activity of GCS is present, and its inhibitors hinder resistance. Resistant cells exhibit cross-resistance, despite differing in marker expression, and cytotoxic mechanism. These findings suggest that GCS protects glioblastoma cells against autophagic and apoptotic death, and contributes to cell survival under chemotherapy.
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