Fomitoside-K from Fomitopsis nigra Induces Apoptosis of Human Oral Squamous Cell Carcinomas (YD-10B) via Mitochondrial Signaling Pathway
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概要
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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.
著者
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Lee In-kyoung
Division Of Biotechnology And Advanced Institute Of Environment And Bioscience College Of Environmental And Bioresource Sciences Chonbuk National University
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Yun Bong-sik
Division Of Biotechnology And Advanced Institute Of Environment And Bioscience College Of Environmental And Bioresource Sciences Chonbuk National University
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Lee In-Kyoung
Division of Biotechnology, College of Environmental & Biosource Science, Chonbuk National University
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Yi Ho-Keun
Department of Oral Biochemistry, Institute of Oral Bioscience, BK21 program, School of Dentistry, Chonbuk National University
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Yun Bong-Sik
Division of Biotechnology, College of Environmental & Biosource Science, Chonbuk National University
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Hwang Pyong-Han
Department of Pediatrics, School of Medicine, Chonbuk National University
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Bhattarai Govinda
Department of Oral Biochemistry, Institute of Oral Bioscience, BK21 program, School of Dentistry, Chonbuk National University
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Lee Young-Hee
Department of Oral Biochemistry, Institute of Oral Bioscience, BK21 program, School of Dentistry, Chonbuk National University
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Lee Nan-Hee
Department of Oral Biochemistry, Institute of Oral Bioscience, BK21 program, School of Dentistry, Chonbuk National University
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