title: Inhibition of glucose transporter 1 induces apoptosis and sensitizes multiple myeloma cells to conventional chemotherapeutic agents.
abstract: Despite the recent development of anti-myeloma drugs, the prognosis of high-risk multiple myeloma remains poor. Therefore, new effective treatment strategies for this disease are needed. It has been reported that high intensity of 18-fluorodeoxyglucose positron emission tomography is high-risk factor in myeloma, suggesting that glucose uptake can be therapeutic target in high-risk myeloma. In this study, we addressed the utility of glucose transporter 1 (GLUT1) as a therapeutic target for myeloma with increased glucose uptake. We found myeloma cell lines with elevated glucose uptake activity via GLUT1 up-regulation. STF-31, a selective GLUT1 inhibitor, completely suppressed the glucose uptake activity and induced apoptosis in GLUT1 expressing myeloma cells. On the other hand, this agent little shows the cytotoxicity in normal peripheral blood mononuclear cells. Moreover, STF-31 synergistically enhanced the cell death induced by melphalan, doxorubicin, and bortezomib. GLUT1 may be promising therapeutic target in myeloma with elevated glucose uptake.
authors.affiliation: Department of Drug Informatics, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan. Electronic address: tmatsumoto@fukuoka-u.ac.jp.
authors.forename: Taichi
authors.initials: T
authors.lastname: Matsumoto
authors.affiliation: Central Laboratory for Pathology and Morphology, Department of Medicine, Fukuoka University, Fukuoka, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Jimi
authors.affiliation: Department of Drug Informatics, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Migita
authors.affiliation: Division of Medical Oncology, Hematology and Infectious Diseases, Department of Medicine, Fukuoka University, Fukuoka, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Takamatsu
authors.affiliation: Department of Drug Informatics, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan.
authors.forename: Shuuji
authors.initials: S
authors.lastname: Hara
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D004357:Drug Synergism; D005947:Glucose / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000037:antagonists & inhibitors*; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D009101:Multiple Myeloma / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology*; D015854:Up-Regulation
chemical_list: D051272:Glucose Transporter Type 1; D011725:Pyridines; C000599307:STF-31; D005947:Glucose
keywords: Glucose metabolism; Glucose transporter 1 (GLUT1); Multiple myeloma