title: Rutin increases the cytotoxicity of temozolomide in glioblastoma via autophagy inhibition.
abstract: The chemotherapeutic agent temozolomide (TMZ) is widely used in the treatment of glioblastoma multiforme (GBM). Rutin, a citrus flavonoid ecglycoside found in edible plants, has neuroprotective and anticancer activities. This study aimed to investigate the efficacy and the underlying mechanisms of rutin used in combination with TMZ in GBM. In vitro cell viability assay demonstrated that rutin alone had generally low cytotoxic effect, but it enhanced the efficacy of TMZ in a dose-dependent manner. Subcutaneous and orthotopic xenograft studies also showed that tumor volumes were significantly lower in mice receiving combined TMZ/Rutin treatment as compared to TMZ or rutin alone treatment. Moreover, immunoblotting analysis showed that TMZ activated JNK activity to induce protective response autophagy, which was blocked by rutin, resulting in decreased autophagy and increased apoptosis, suggesting that rutin enhances TMZ efficacy both in vitro and in vivo via inhibiting JNK-mediated autophagy in GBM. The combination rutin with TMZ may be a potentially useful therapeutic approach for GBM patient.
authors.affiliation: Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Pingde
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Stella
authors.initials: S
authors.lastname: Sun
authors.affiliation: Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Amy Suk Wai
authors.initials: ASW
authors.lastname: Ho
authors.affiliation: Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Karrie Mei Yee
authors.initials: KMY
authors.lastname: Kiang
authors.affiliation: Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Yin Stephen
authors.initials: YS
authors.lastname: Cheng
authors.affiliation: Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Ming Wai
authors.initials: MW
authors.lastname: Poon
authors.affiliation: Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Derek
authors.initials: D
authors.lastname: Lee
authors.affiliation: Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Jenny Kan Suen
authors.initials: JKS
authors.lastname: Pu
authors.affiliation: Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China. gilberto@hku.hk.
authors.forename: Gilberto Ka Kit
authors.initials: GKK
authors.lastname: Leung
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D001932:Brain Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000494:pharmacology; D004357:Drug Synergism; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D012431:Rutin / Q000494:pharmacology*; D000077204:Temozolomide; D023041:Xenograft Model Antitumor Assays
chemical_list: D012431:Rutin; D003606:Dacarbazine; D000077204:Temozolomide
keywords: Apoptosis; Autophagy; Glioblastoma multiforme; Rutin; Temozolomide