title: Caspase-dependent signaling underlies glioblastoma cell death in response to the fungal metabolite, fusarochromanone.
abstract: Fungal metabolites continue to show promise as a viable class of anticancer agents. In the present study, we investigated the efficacy of the fungal metabolite, fusarochromanone (FC101), for its antitumor activities in glioblastomas, which have a median survival of less than two years and a poor clinical response to surgical resection, radiation therapy and chemotherapy. Using clinically applicable doses, we demonstrated that FC101 induced glioblastoma apoptotic cell death via caspase dependent signaling, as indicated by the cleavage of poly(ADP-ribose) polymerase, glioblastoma (PARP). FC101 also induced differential reactive oxygen species (ROS) levels in glioblastoma cells, contrasting a defined role of oxidative stress in apoptotic cell death observed with other fungal metabolites. Furthermore, the antitumorigenic effects of FC101 on tumor cell migration were assessed. Cell migration assays revealed that FC101 significantly reduced the migratory capacity of glioblastomas, which are incredibly invasive tumors. Taken together, the present study establishes FC101 as a candidate anticancer agent for the cooperative treatment of glioblastomas.
authors.affiliation: Department of Chemistry and Physics, LSU-Shreveport, Shreveport, LA 71115, USA.
authors.forename: Elahe
authors.initials: E
authors.lastname: Mahdavian
authors.affiliation: Department of Biological Sciences, Tennessee State University, Nashville, TN 37209, USA.
authors.forename: Monique
authors.initials: M
authors.lastname: Marshall
authors.affiliation: Department of Biology, North Carolina A&T State University, Greensboro, NC 27411, USA.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Martin
authors.affiliation: Department of Biology, North Carolina A&T State University, Greensboro, NC 27411, USA.
authors.forename: Patrice
authors.initials: P
authors.lastname: Cagle
authors.affiliation: Department of Chemistry and Physics, LSU-Shreveport, Shreveport, LA 71115, USA.
authors.forename: Brian A
authors.initials: BA
authors.lastname: Salvatore
authors.affiliation: Department of Biological Sciences, Tennessee State University, Nashville, TN 37209, USA.
authors.forename: Quincy A
authors.initials: QA
authors.lastname: Quick
mesh_terms: D000185:Actinin / Q000378:metabolism; D001932:Brain Neoplasms / Q000201:enzymology* / Q000473:pathology*; D020169:Caspases / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005909:Glioblastoma / Q000201:enzymology* / Q000473:pathology*; D006801:Humans; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors
chemical_list: D002867:Chromones; D017382:Reactive Oxygen Species; D000185:Actinin; D020169:Caspases; C054523:fusarochromanone