title: Cordyceps militaris and mycelial fermentation induced apoptosis and autophagy of human glioblastoma cells.
abstract: This study is the first report that investigated the apoptosis-inducing effects of Cordyceps militaris (CM) and its mycelial fermentation in human glioblastoma cells. Both fractions arrested the GBM8401 cells in the G0/G1 phase, whereas the U-87MG cells were arrested at the G2/M transitional stage. Western blot data suggested that upregulation of p53 and p21 might be involved in the disruption of cell cycle progression. Induction of chromosomal condensation and the appearance of a sub-G1 hypodipoid population further supported the proapoptogenicity, possibly through the activation of caspase-3 and caspase-8, and the downregulation of antiapoptotic Bcl-2 and the upregulation of proapoptotic Bax protein expression. Downregulation of mammalian target of rapamycin and upregulation of Atg5 and LC3 II levels in GBM8401 cells implicated the involvement of autophagy. The signaling profiles with mycelial fermentation treatment indicated that mycelial fermentation triggered rapid phosphorylation of Akt, p38 MAPK, and JNK, but suppressed constitutively high levels of ERK1/2 in GBM8401 cells. Mycelial fermentation treatment only significantly increased p38 MAPK phosphorylation, but decreased constitutively high levels of Akt, ERK1/2, and JNK phosphorylation in U-87MG cells. Pretreatment with PI3K inhibitor wortmannin and MEK1 inhibitor PD98059 prevented the mycelial fermentation-induced cytotoxicity in GBM8401 and U-87MG cells, suggesting the involvement of PI3K/Akt and MEK1 pathways in mycelial fermentation-driven glioblastoma cell apoptosis and autophagy.
authors.affiliation: Department of Biological Science and Technology, I-Shou University, Kaohsiung, Taiwan.
authors.forename: C-H
authors.initials: CH
authors.lastname: Yang
authors.forename: Y-H
authors.initials: YH
authors.lastname: Kao
authors.forename: K-S
authors.initials: KS
authors.lastname: Huang
authors.forename: C-Y
authors.initials: CY
authors.lastname: Wang
authors.forename: L-W
authors.initials: LW
authors.lastname: Lin
mesh_terms: D017209:Apoptosis; D001343:Autophagy; D001685:Biological Factors / Q000378:metabolism / Q000494:pharmacology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D032661:Cordyceps / Q000737:chemistry* / Q000254:growth & development / Q000378:metabolism; D005285:Fermentation; D005909:Glioblastoma / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D025282:Mycelium / Q000737:chemistry / Q000254:growth & development / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism
chemical_list: D001685:Biological Factors; D019253:Proto-Oncogene Proteins c-bcl-2; D048031:JNK Mitogen-Activated Protein Kinases