title: Fomitoside-K from Fomitopsis nigra induces apoptosis of human oral squamous cell carcinomas (YD-10B) via mitochondrial signaling pathway.
abstract: In this study, a new lanostane triterpene glycoside (fomitoside-K) having biologically active molecules was isolated from a mushroom Fomitopsis nigra to test its anticancer activity on human oral squamous cell carcinomas (YD-10B). We focused on the effect of fomitoside-K on apoptosis, the mitochondria-mediated death pathway and the accumulation of reactive oxygen species (ROS) in YD-10B cells. Fomitoside-K could induce a dose and time-dependent apoptosis in YD-10B cells as characterized by cell morphology, cell cycle arrest, inhibition of survivin, activation of poly(ADP-ribose) polymerase (PARP), caspase-3, -9 and an increased expression ratio of Bax/Bcl-2. The mitochondria membrane potential loss and cytochrome c (Cyt C) release from mitochondria to cytosol were observed during the induction. Moreover, fomitoside-K caused dose-dependent elevation of intracellular ROS level and increase phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) in YD-10B cells. To further investigate the mechanisms, we examined the effects of ROS scavenger N-acetyl-L-cysteine (NAC) and selective inhibitors for mitogen activated protein kinase (MAPK) pathways on the cell death. The fomitoside-K induced cell death by ROS was significantly inhibited by NAC, ERK (PD98059) and JNK inhibitor (SP600125). In addition, fomitoside-K has a synergistic effect with adriamycin in suppressing the growth of YD-10B cells. These data suggest that fomitoside-K induces apoptosis in YD-10B cells through the ROS-dependent mitochondrial dysfunction pathway and provides a mechanistic framework for further exploring the use of fomitoside-K against the proliferation of human oral cancer.
authors.affiliation: Department of Oral Biochemistry, Institute of Oral Bioscience, BK21 Program, School of Dentistry, Chonbuk National University, Korea.
authors.forename: Govinda
authors.initials: G
authors.lastname: Bhattarai
authors.forename: Young-Hee
authors.initials: YH
authors.lastname: Lee
authors.forename: Nan-Hee
authors.initials: NH
authors.lastname: Lee
authors.forename: In-Kyoung
authors.initials: IK
authors.lastname: Lee
authors.forename: Bong-Sik
authors.initials: BS
authors.lastname: Yun
authors.forename: Pyong-Han
authors.initials: PH
authors.lastname: Hwang
authors.forename: Ho-Keun
authors.initials: HK
authors.lastname: Yi
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002294:Carcinoma, Squamous Cell; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D055453:Coriolaceae; D019938:Cyclin D1 / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D006027:Glycosides; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009062:Mouth Neoplasms; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014315:Triterpenes; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C494826:BAX protein, human; D006027:Glycosides; D017382:Reactive Oxygen Species; D014315:Triterpenes; D051028:bcl-2-Associated X Protein; C578582:fomitoside-K; D019938:Cyclin D1; D045304:Cytochromes c; D020928:Mitogen-Activated Protein Kinases; D053148:Caspase 3; D053453:Caspase 9