title: Glucopsychosine increases cytosolic calcium to induce calpain-mediated apoptosis of acute myeloid leukemia cells.
abstract: To identify novel anti-cancer agents, we created and screened a unique nutraceutical library for activity against acute myeloid leukemia (AML) cells. From this screen, we determined that glucopsychosine was selectively toxic toward AML cell lines and primary AML patient samples with no effect toward normal hematopoietic cells. It delayed tumor growth and reduced tumor weights in mouse xenograft models without imparting toxicity. Glucopsychosine increased cytosolic calcium and induced apoptosis through calpain enzymes. Extracellular calcium was functionally important for glucopsychosine-induced AML cell death and surface calcium channel expression is altered in AML cells highlighting a unique mechanism of glucopsychosine's selectivity.
authors.affiliation: School of Pharmacy, University of Waterloo, 10A Victoria Street, Kitchener, Ontario N2G 1C5, Canada.
authors.forename: Leonard
authors.initials: L
authors.lastname: Angka
authors.affiliation: School of Pharmacy, University of Waterloo, 10A Victoria Street, Kitchener, Ontario N2G 1C5, Canada.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Lee
authors.affiliation: School of Pharmacy, University of Waterloo, 10A Victoria Street, Kitchener, Ontario N2G 1C5, Canada.
authors.forename: Sarah G
authors.initials: SG
authors.lastname: Rota
authors.affiliation: School of Pharmacy, University of Waterloo, 10A Victoria Street, Kitchener, Ontario N2G 1C5, Canada.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hanlon
authors.affiliation: Advanced Molecular Diagnostics Laboratory, Department of Pathology, University Health Network, Toronto, Ontario M5G 2M9, Canada.
authors.forename: Mahadeo
authors.initials: M
authors.lastname: Sukhai
authors.affiliation: Princess Margaret Cancer Center, Ontario Cancer Institute, 610 University Ave, Toronto, Ontario M5G 2M9, Canada.
authors.forename: Mark
authors.initials: M
authors.lastname: Minden
authors.affiliation: Department of Kinesiology, University of Waterloo, 200 University Ave. W., Waterloo, Ontario N2L 3G1, Canada.
authors.forename: Elliott M
authors.initials: EM
authors.lastname: McMillan
authors.affiliation: Department of Kinesiology, University of Waterloo, 200 University Ave. W., Waterloo, Ontario N2L 3G1, Canada.
authors.forename: Joe
authors.initials: J
authors.lastname: Quadrilatero
authors.affiliation: School of Pharmacy, University of Waterloo, 10A Victoria Street, Kitchener, Ontario N2G 1C5, Canada. Electronic address: paul.spagnuolo@uwaterloo.ca.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Spagnuolo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002154:Calpain / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D011609:Psychosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D015220:Calcium Channels; D011609:Psychosine; C035742:sphingosyl beta-glucoside; D002154:Calpain; D002118:Calcium
keywords: Acute myeloid leukemia; Calcium; Calpain; Glucopsychosine; Nutraceuticals