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.

Glucosylceramide Synthase protects Glioblastoma cells against autophagic and apoptotic death induced by temozolomide and paclitaxel / P. Giussani, R. Bassi, V. Anelli, L. Brioschi, F. De Zen, E. Riccitelli, M. Caroli, R. Campanella, S.M. Gaini, P. Viani, L. Riboni. - In: CANCER INVESTIGATION. - ISSN 0735-7907. - 30:1(2012), pp. 27-37.

Glucosylceramide Synthase protects Glioblastoma cells against autophagic and apoptotic death induced by temozolomide and paclitaxel

P. Giussani
Primo
;
R. Bassi
Secondo
;
L. Brioschi;E. Riccitelli;S.M. Gaini;P. Viani
Penultimo
;
L. Riboni
2012

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.
Autophagy; Ceramide; Glioblastoma; Glucosylceramide synthase; Temozolomide
Settore BIO/10 - Biochimica
Settore MED/26 - Neurologia
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/169052
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