title: Glucosylceramide synthase protects glioblastoma cells against autophagic and apoptotic death induced by temozolomide and Paclitaxel.
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.
authors.affiliation: Department of Medical Chemistry, Biochemistry and Biotechnology, LITA-Segrate, University of Milan, Milan, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Giussani
authors.forename: R
authors.initials: R
authors.lastname: Bassi
authors.forename: V
authors.initials: V
authors.lastname: Anelli
authors.forename: L
authors.initials: L
authors.lastname: Brioschi
authors.forename: F
authors.initials: F
authors.lastname: De Zen
authors.forename: E
authors.initials: E
authors.lastname: Riccitelli
authors.forename: M
authors.initials: M
authors.lastname: Caroli
authors.forename: R
authors.initials: R
authors.lastname: Campanella
authors.forename: S M
authors.initials: SM
authors.lastname: Gaini
authors.forename: P
authors.initials: P
authors.lastname: Viani
authors.forename: L
authors.initials: L
authors.lastname: Riboni
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D016543:Central Nervous System Neoplasms / Q000188:drug therapy / Q000378:metabolism; D002518:Ceramides / Q000378:metabolism; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000502:physiology; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism; D005964:Glucosyltransferases / Q000378:metabolism*; D006801:Humans; D017239:Paclitaxel / Q000494:pharmacology*; D000077204:Temozolomide
chemical_list: D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D000972:Antineoplastic Agents, Phytogenic; D002518:Ceramides; D003606:Dacarbazine; D005964:Glucosyltransferases; C023246:ceramide glucosyltransferase; D017239:Paclitaxel; D000077204:Temozolomide