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Cancer Invest. 2012 Jan;30(1):27-37. doi: 10.3109/07357907.2011.629379.

Glucosylceramide synthase protects glioblastoma cells against autophagic and apoptotic death induced by temozolomide and Paclitaxel.

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1
Department of Medical Chemistry, Biochemistry and Biotechnology, LITA-Segrate, University of Milan, Milan, Italy.

Abstract

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.

PMID:
22236187
DOI:
10.3109/07357907.2011.629379
[Indexed for MEDLINE]
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